WORLDSymposium™ 2019 Full Program on Lysosomal Diseases

Monday, Feb. 4 Tuesday, Feb. 5 Wednesday, Feb. 6 Thursday, Feb. 7

9:00 – 12:00	Council of Patient Advocates (COPA) Workshop: WORLDFair^™	The Lysosomal Disease Network (LDN) Annual Council of Patient Advocates (COPA) Meeting
1:00 – 5:00	Pre-Conference Symposium	Emerging Trends: State-of-the-Art for Experts (Registration required)
5:15	Young Investigator Award Ceremony	Young Investigator Awards Presented. Regency Foyer.
5:30 – 6:30	Opening Reception	Regency Ballroom R (Exhibit Hall) – Open to all attendees
6:30	Satellite Symposia

Basic and bench research. Following the presentation of the Roscoe O. Brady Award for Innovation and Accomplishment in lysosomal disease research, presentations in the morning and afternoon sessions discussed innovations in technology and how they can be applied to early diagnosis for lysosomal conditions, progress in gene therapy, and exploitation of differences at the cellular level that may indicate early disease state. After the presentations ended at 4:30, the evening poster sessions opened. Abstracts from over 175 researchers were presented on Day 1, primarily focused on basic and translational research. Download the WORLDSymposium 2019 program (PDF 175KB).

Basic Science I: Disease Mechanisms, Pathology, and Biomarkers of Lysosomal Diseases

Co-Chairs: Danilo A. Tagle & Cynthia J. Tifft

6:15	Satellite Symposia
7:30	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome & Announcements Presentation of 2019 Roscoe O. Brady Award for Innovation and Accomplishment
7:45	Danilo A. Tagle National Center for Advancing Translational Sciences National Institutes of Health Bethesda, MD, United States	2019 Roscoe O. Brady Award for Innovation and Accomplishment
8:15	Eric Joshua Garcia National Institutes of Health Bethesda, MD, United States	Methylomic and whole transcriptome analyses reveal several potential modifier genes in GBA1-associated Parkinson disease
8:30	Vera Niederkofler QPS Austria GmbH Grambach, Austria	CBE treatment of alpha-synuclein over-expressing and wildtype mice models Gaucher disease pathology
8:45	Annalisa Astolfi University of Bologna Bologna, Italy	Hippo and necroptosis pathways are involved in cell growth defects in Gaucher disease
9:00	Pilar Giraldo Institute of Health Research Aragon (IIS Aragón) Zaragoza, Spain	Strain-elastography in musculoskeletal evaluation in Gaucher disease
9:15	Amelia Ahern-Rindell University of Portland Portland, OR, United States	Design and analysis of a CRISPR gene editing strategy in a sheep model variant of GM1-gangliosidosis
9:30	Anatalia Labilloy Cincinnati Children’s Hospital Medical Center Cincinnati, OH, United States	Proteomic profiling of engineered human immortalized podocyte cell model of Fabry disease
9:45	Break & Exhibits
10:15	Behzad Najafian University of Washington Seattle, WA, United States	A novel method for quantification of globotriaocylceramide (GL-3) inclusions in affected podocytes in females with Fabry disease shows progressive accumulation of GL-3 in podocytes with age and no cross-correction between affected and non-affected podocytes
10:30	Jin-Song Shen Baylor Research Institute Dallas, TX, United States	Dysregulated DNA methylation in the pathogenesis of Fabry disease
10:45	Siamak Jabbarzadeh-Tabrizi Baylor Research Institute Dallas, TX, United States	Effects of genetic background on disease phenotypes in a mouse model of Fabry disease
11:00	Pasqualina Colella Généthon, Université Evry, Université Paris Saclay Evry, France	Latent TGF-beta-binding protein 4 modulates disease severity in the knock-out mouse model of Pompe disease
11:15	Katie Harvey Great Ormond Street Hospital London, United Kingdom	The evolving role of enzymology and metabolomics in the diagnosis of lysosomal disorders in the post genomic era
11:30	Lunch – On Own or Satellite Symposia	Exhibit Hall Open
11:45	Satellite Symposia

Basic Science II: Developing Therapeutic Approaches for Lysosomal Diseases in the Laboratory

Co-Chairs: David A. Pearce & Tiina K. Urv

1:00	Virginia Kimonis University of California – Irvine Orange, CA, United States	Antisense oligonucleotide treatment targeting glycogen synthase (GYS1) in a mouse model of Pompe disease
1:15	Kohji Itoh Tokushima University Tokushima, Japan	In vivo gene therapy for Tay-Sachs and Sandhoff diseases by utilizing AAV9 vector encoding modified HEXB
1:30	Kazuki Sawamoto Nemours/Alfred I. duPont Hospital for Children Wilmington, DE, United States	Development of AAV gene therapy for Morquio syndrome type A
1:45	Saida Ortolano Instituto de Investigación Sanitaria Galicia Sur Vigo (Pontevedra), Spain	Functional evaluation of an AAV9 based vector expressing alpha-galactosidase A for potential gene therapy of Fabry disease
2:00	Xin Chen University of Texas Southwest Medical Center Dallas, TX, United States	Therapeutic efficacy and safety of scAAV9/AGA gene therapy in aspartylglucosaminuria mice
2:15	Murtaza S. Nagree University of Toronto Toronto, ON, Canada	Lentiviral-modified T Rapa cells as ‘micropharmacies’ for lysosomal diseases
2:30	Hojun Choi Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Korea	Exosome-mediated delivery of active glucocerebrosidase to Gaucher model cells
2:45	Break & Exhibits
3:15	Ibane Abasolo Vall d’Hebron Institute of Research Barcelona, Spain	Targeted nanoliposomes for the treatment of Fabry disease
3:30	Cristin Davidson National Institutes of Health Bethesda, MD, United States	Improved disease amelioration with combination therapy for Niemann-Pick type C1 disease
3:45	Yanyan Peng Cincinnati Children’s Hospital Medical Center Cincinnati, OH, United States	Intravenous infusion of iPSC-derived neural progenitors expressing GCase ameliorates alpha-synuclein aggregates in a mouse model of Gaucher disease
4:00	Jeanine R. Jarnes University of Minnesota Minneapolis, MN, United States	Chitotriosidase as a biomarker for central nervous system inflammation in the gangliosidosis diseases
4:15	Chloe L. Christensen University of Victoria Victoria, BC, Canada	Delivery of adenine base editors to patient-derived induced pluripotent stem cells in vitro: A putative treatment for mucopolysaccharidosis type IIIB
4:30	Poster Reception in the Exhibit Hall	Poster presenters with First Author Last Name starting with A-L displayed
6:30	Satellite Symposia

Translational research. The second day of the meeting turned to the challenge of moving laboratory discoveries to therapy, the important hurdles of translational research. Some broad topics of discussion included gene therapy, newborn screening, modulation of CNS affects of disease, how to increase the efficacy of therapeutic modalities, and genotype/phenotype correlations. After the presentations ended at 4:30 on Day 2, a second set of poster abstracts were presented by more than 200 additional researchers, featuring cutting-edge translational and clinical research areas. Download the WORLDSymposium 2019 program (PDF 175KB).

Translational Research IA: Gene Therapy

Co-Chairs: R. Scott McIvor & Mark S. Sands

6:15	Satellite Symposia
7:30	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	2019 Patient Advocate Leader Announcement and Presentation to Mark Dant
7:45	Steven J. Gray University of Texas Southwestern Medical Center Dallas, TX, United States	Intrathecal and intravenous combination gene therapy in the mouse model of infantile neuronal ceroid lipofuscinosis extends lifespan and improves behavioral outcomes in moderately affected mice
8:00	Raymond Y. Wang Children’s Hospital of Orange County Orange, CA, United States	Intra-articular AAV9 α-iduronidase gene therapy in the canine model of mucopolysaccharidosis type I results in rapid synovial and cartilage iduronidase expression, clearance of heparan sulfate, and high serum α-iduronidase levels
8:15	Roselena S. Schuh Universidade Federal do Rio Grande do Sul Porto Alegre, Brazil	Newborn genome editing improves phenotype, cardiovascular, respiratory, and bone disease in mucopolysaccharidosis type I mice
8:30	Brian Bigger University of Manchester Manchester, United Kingdom	Brain targeted stem cell gene therapy provides long-term correction of mucopolysaccharidosis type II
8:45	Giuseppe Ronzitti Généthon, Université of Evry, Université Paris-Saclay Evry, France	Safety and efficacy evaluation of investigational liver gene transfer for secretable GAA in the treatment of Pompe disease
9:00	Jeffrey A. Medin Medical College of Wisconsin Milwaukee, WI, United States	FACTs Fabry gene therapy clinical trial: Two year data
9:15	Kevin M. Flanigan Center for Gene Therapy, Nationwide Children’s Hospital Columbus, OH, United States	Phase 1/2 clinical trial of systemic gene transfer of scAAV9.U1a.hSGSH for MPS IIIA demonstrates 2 years of safety, tolerability, and biopotency
9:30	Cassie Bebout Auburn University Auburn, AL, United States	Analysis of the effect of intravenous gene therapy on brain and peripheral disease in a feline model of GM1-gangliosidosis
9:45	Break & Exhibits

Translational Research IB: Implementation and Impact of Newborn Screening

Co-Chairs: Amy Gaviglio & Priya Kishnani

10:15	Chia-Feng Yang Taipei Veterans General Hospital Taipei City, Taiwan	Very early treatment for infantile-onset Pompe disease contributes to better outcomes: 10-year experience of nationwide NBS in Taiwan
10:30	Barbara K. Burton Ann & Robert H. Lurie Children’s Hospital Chicago, IL, United States	Newborn screening for mucopolysaccharidosis type II (MPS II) in Illinois: The first year’s experience
10:45	Elizabeth Braunlin University of Minnesota Minneapolis, MN, United States	Hematopoietic cell transplantation for severe MPS I in the first six months of life: The heart of the matter
11:00	Adam Guenzel Mayo Clinic Rochester, MN, United States	Improved differentiation between Krabbe disease variants, carrier status, and pseudo deficiency by measurement of psychosine
11:15	Francisco J. del Castillo Hospital Universitario Ramón y Cajal, IRYCIS Madrid, Spain	NGS-based, 107-gene resequencing panel as first-line screening test for lysosomal diseases
11:30	Lunch – On Own or Satellite Symposia	Exhibit Hall Open
11:45	Satellite Symposia

Translational Research II: Clinical Trial Readiness – Pre-Clinical Trial Methods and Studies

Co-Chairs: Lalitha R. Belur & Philip J. Brooks

1:00	Laura Adang Children’s Hospital of Philadelphia Philadelphia, PA, United States	Clinical presentation of metachromatic leukodystrophy
1:15	Cara O’Neill Cure Sanfilippo Foundation Columbia, SC, United States	The natural history of facial features observed in Sanfilippo syndrome (MPS IIIB) using a next generation phenotyping tool
1:30	Rebecca Ahrens-Nicklas The Children’s Hospital of Philadelphia Philadelphia, PA, United States	A natural history study of multiple sulfatase deficiency
1:45	Lynda E. Polgreen Los Angeles Biomedical Research Institute at Harbor-UCLA Torrance, CA, United States	Exploring surrogate biomarkers of skeletal and joint disease progression in mucopolysaccharidosis type I
2:00	Shunji Tomatsu Nemours/Alfred I. duPont Hospital for Children Wilmington, DE, United States	Effect of enzyme replacement therapy on the growth of patients with Morquio syndrome type A
2:15	Ankit K. Desai Duke University Durham, NC, United States	Changing the clinical course of infantile Pompe disease with immune modulation strategies: 12 years of experience
2:30	Simon Heales Great Ormond Street Hospital/UCL London, United Kingdom	Urinary glucose tetrasaccharide, a useful prognostic biomarker for Pompe disease?
2:45	Break & Exhibits
3:15	Quoc-Hung Nguyen University of California – San Francisco San Francisco, CA, United States.	Fetal enzyme replacement and stem cell transplantation in murine Sly syndrome targeting microglia
3:30	Igor Nestrasil University of Minnesota Minneapolis, MN, United States	Discovery of brain MRI signatures in infants with severe form of MPS I in the pre-HSCT and post-HSCT stages
3:45	Adeline Vanderver Children’s Hospital of Philadelphia Philadelphia, PA, United States	Intrathecally administered recombinant human arylsulfatase A in patients with late-infantile metachromatic leukodystrophy: Phase 2b clinical trial design
4:00	Reena V. Kartha University of Minnesota Minneapolis, MN, United States	Preliminary N-acetylcysteine results for LDN 6722, Role of oxidative stress and inflammation in Gaucher disease type 1: Potential use of antioxidant anti-inflammatory medications
4:15	Eric K.W. Hui ArmaGen Inc. Calabasas, CA, United States	Preclinical studies of a brain penetrating IgG trojan horse-arylsulfatase fusion protein in the metachromatic leukodystrophy mouse
4:30	Poster Reception in the Exhibit Hall	Poster presenters with First Author Last Name starting with M-Z and all Late-Breaking abstracts displayed
6:30	Satellite Symposia

Clinical research. The entire third day of WORLDSymposium was committed to presentations of results from clinical trials, which in most cases is the actual application of new agents in humans affected by these conditions. Day 3 also included presentations related to re-thinking the definition of biomarkers for lysosomal disease. Download the WORLDSymposium 2019 program (PDF 175KB).

Clinical Trials I: Clinical Trials for Registration

Co-Chairs: Stephen C. Groft & Anne R. Pariser

6:15	Satellite Symposia
7:30	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Keynote Address: The ‘new’ Lysosomal Disease Network
8:00	Raphael Schiffmann Baylor Research Institute Dallas, TX, United States	Venglustat in adult Gaucher disease type 3: Preliminary safety, pharmacology, and exploratory efficacy from a phase 2 trial in combination with imiglucerase (LEAP)
8:15	Ronald G. Crystal Weill Cornell Medicine New York, NY, United States	Design and rationale of the LYS-SAF302 gene therapy study in mucopolysaccharidosis type IIIA (MPS IIIA) children
8:30	Myrl D. Holida University of Iowa Hospitals and Clinics Iowa City, IA, United States	Once every 4 weeks – 2 mg/kg of pegunigalsidase alfa for treating Fabry disease; Preliminary results of a phase 3 study
8:45	Ulla Feldt-Rasmussen Rigshospitalet, Copenhagen University Hospital Copenhagen, Denmark	Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 30-month results from the randomized phase 3 ATTRACT study
9:00	Priya S. Kishnani Duke University Durham, NC, United States	Safety and efficacy of VAL-1221, a novel fusion protein targeting cytoplasmic glycogen, in patients with late-onset Pompe disease
9:15	Paula R. Clemens University of Pittsburgh and Department of Veterans Affairs Medical Center Pittsburgh, PA, United States	Efficacy and safety of AT-GAA (ATB200/AT2221) in ERT-switch non-ambulatory patients with Pompe disease: Preliminary results from the ATB200-02 trial
9:30	Loren Pena University of Cincinnati College of Medicine Cincinnati, OH, United States	NEO1 and NEO-EXT studies: Long-term safety of repeat avalglucosidase alfa dosing for 4.5 years in late-onset Pompe disease patients
9:45	Refreshment Break in Foyer
10:15	Nathalie Guffon Hôpital Femme Mère Enfant Lyon, France	The first study investigating safety and efficacy of velmanase alfa (human recombinant alpha mannosidase) in alpha-mannosidosis patients below six years of age
10:30	Kara Woolgar Phoenix Children’s Hospital Phoenix, AZ, United States	Intravenous 2-hydroxypropyl-beta-cyclodextrin for a Niemann-Pick disease type C1 infant with liver cirrhosis
10:45	Paul J. Orchard University of Minnesota Minneapolis, MN, United States	Preliminary results demonstrate engraftment with minimal neutropenia with MGTA-456, a CD34⁺ expanded cord blood (CB) product in patients transplanted for inherited metabolic disorders (IMD)
11:00	Joseph Muenzer University of North Carolina, Chapel Hill Chapel Hill, NC, United States	CHAMPIONS: A phase 1/2 clinical trial with dose escalation of SB-913 ZFN-mediated in vivo human genome editing for treatment of MPS II (Hunter syndrome)
11:15	Paul Harmatz UCSF Benioff Children’s Hospital Oakland Oakland, CA, United States	EMPOWERS: A phase 1/2 clinical trial of SB-318 ZFN-mediated in vivo human genome editing for treatment of MPS I (Hurler syndrome)
11:30	Lunch – On Own or Satellite Symposia
11:45	Satellite Symposia

Clinical Trials II: Clinical Outcomes

Co-Chairs: Yoshikatsu Eto, Jill Morris & Marc C. Patterson

1:00	Maureen Cleary Great Ormond Street Hospital London, United Kingdom	ICV-administered tralesinidase alfa (BMN 250; NAGLU-IGF2) is well-tolerated and reduces heparan sulfate accumulation in the CNS of subjects with Sanfilippo syndrome type B (MPS IIIB)
1:15	Maria L. Escolar Children’s Hospital of Pittsburgh Pittsburgh, PA, United States	Long-term neurodevelopmental outcomes of hematopoietic stem cell transplantation for late-infantile Krabbe disease
1:30	Karolina M. Stepien Salford Royal NHS Foundation Trust Salford, United Kingdom	Hormonal dysfunction in adult patients with mucopolysaccharidosis type I post haematopoietic stem cell transplantation
1:45	Ashish Gupta University of Minnesota Minneapolis, MN, United States	Allogeneic hematopoietic stem cell transplant improves outcomes in fucosidosis
2:00	Mark Roberts Salford Royal NHS Foundation Trust Salford, United Kingdom	Preliminary patient-reported outcomes and safety of AT-GAA (ATB200/AT2221) in patients with Pompe disease from the ATB200-02 trial
2:15	Edwin Chavez-Cintora BioMarin Pharmaceutical Inc. Novato, CA, United States	Insights into Sanfilippo syndrome provided by the ConnectMPS worldwide online registry
2:30	Troy Lund University of Minnesota Minneapolis, MN, United States	Predicting intelligence in MPS IH with biomarkers
2:45	Refreshment Break
3:15	Brianna Glase National Institutes of Health Bethesda, MD, United States	Robust clinical outcome measures for patients with juvenile onset GM1-gangliosidosis
3:30	Angela Schulz University Medical Center Hamburg-Eppendorf Hamburg, Germany	Persistent treatment effect of cerliponase alfa in children with CLN2 disease: A 3 year update from an ongoing multicenter extension study
3:45	Tama Dinur Shaare Zedek Medical Center, Hadassah Medical Center, The Hebrew University Jerusalem, Israel	Long-term follow-up of 103 untreated adult patients with type 1 Gaucher disease
4:00	Uma Ramaswami Royal Free London NHS Foundation Trust University College London London, United Kingdom	Migalastat: Single centre experience of adult patients with Fabry disease from the Royal Free London NHS Foundation Trust, UK
4:15	Christian J. Hendriksz Steve Biko Academic Hospital Pretoria, South Africa	Evidence-based, expert-agreed recommendations for the management of patients with MPS IVA/VI: Recommendations to replace the specific missing enzyme
4:30	Adjourn & Networking Reception	Open to All Attendees; Regency Rotunda
5:30	Council of Research Experts (CORE) Meeting	The Lysosomal Disease Network (LDN) annual Council of Research Experts (CORE) meeting for NIH-funded investigators

2019 Emerging Trends in Lysosomal Biology & Lysosomal Diseases: State-of-the-art for Experts

Monday, February 4, 2019 from 1:00 – 5:00 PM

For the seventh consecutive year, WORLDSymposium™ began with “Emerging Trends” on Monday afternoon, February 4, 2019 at 1:00 PM. This 4-hour CME course provided a state-of-the-art update for experts working in lysosomal biology and lysosomal diseases. This course was a summary of the latest research trends and other advances in the field.

Seasoned researchers provided a global review of the past years’ advances, a state-of-the-art overview of lysosome biology, diseases and therapies. This review evolves every year, providing a summary of the latest research trends, new knowledge, and other discoveries. The course was intended for researchers and health care practitioners who are interested in being current on recent advances in the basic science, diagnosis, and treatment of lysosomal diseases. This course was taught at the postgraduate level, e.g., those with a PhD, MD, PharmD, DDS, MS, MPH, etc.

The content provided comprehensive information on lysosomal diseases, but does not overlap or replace the scientific data being presented during WORLDSymposium 2019. Registration Required.

Learning Objectives

Upon completion of this educational activity, the participant should be better able to:

Describe the basic structure, function and molecular biology of lysosomes.
Identify specific lysosomal diseases, their clinical manifestations, and means of diagnosis.
Review current treatments for lysosomal diseases, the potential side effects, and their expected clinical outcomes.
Correlate the molecular biology of lysosomes with clinical features, diagnostic testing, and treatment approaches.

Preliminary Agenda

1:00 PM
Introduction and Overview of Course
Chester B. Whitley, PhD, MD

1:10 PM
Lysosomal Disease Phenotypes
Chester B. Whitley, PhD, MD

1:35 PM
Normal Lysosomal Function
Steven U. Walkley, DVM, PhD

2:00 PM
Break

2:05 PM
Remarkable Cases I
Marc C. Patterson, MD

2:30 PM
Lysosomal Disease Pathogenesis
Steven U. Walkley, DVM, PhD

2:55 PM
Refreshment Break

3:10 PM
Current Treatments for Lysosomal Diseases
Jeanine R. Jarnes, PharmD

3:35 PM
Newborn Screening
Amy Gaviglio, MS, LCGC

4:00 PM
Break

4:05 PM
Future Treatments for Lysosomal Diseases
Jeanine R. Jarnes, PharmD

4:30 PM
Remarkable Cases II
Marc C. Patterson, MD

4:55 PM
Final Evaluation
Chester B. Whitley, PhD, MD

5:00 PM
Adjourn

Invited Faculty

Chair: Chester B. Whitley, PhD, MD
Course Director
WORLDSymposium and “Emerging Trends: State-of-the-Art for Experts”
Professor, Department of Pediatrics, and
Experimental and Clinical Pharmacology
University of Minnesota
Principal Investigator, Lysosomal Disease Network
Minneapolis, MN, USA

Steven U. Walkley, DVM, PhD
Director, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center
Head, Sidney Weisner Laboratory of Genetic Neurological Disease
Departments of Neuroscience, Pathology and Neurology
Rose F. Kennedy Center
Albert Einstein College of Medicine
Bronx, NY, USA

Marc C. Patterson, MD, FRACP
Professor of Neurology, Pediatrics and Medical Genetics
Editor-in-Chief, Journal of Child Neurology and Child Neurology Open
Editor, Journal of Inherited Metabolic Disease and JIMD Reports
Mayo Clinic Children’s Center
Rochester, MN, USA

Jeanine R. Jarnes, PharmD, BCOP, BCPS
Adjunct Assistant Professor, Experimental and Clinical Pharmacology
College of Pharmacy
University of Minnesota, Fairview
Minneapolis, MN, USA

Amy Gaviglio, MS, LCGC
Follow-Up Supervisor and Licensed Genetic Counselor
Newborn Screening Program
Minnesota Department of Health
St. Paul, MN

2019 WORLDSymposium Young Investigator Awards Announced

Congratulations to the ten individuals who received the WORLDSymposium Young Investigator Award for 2019. The award was a partial scholarship towards attendance at WORLDSymposium 2019. Numerous individuals submitted an application for the award, and the review process was difficult due to the excellent caliber of all the applicants.

WORLDSymposium would like to congratulate all of the applicants for their hard work. The following individuals received the WORLDSymposium Young Investigator Award for 2019 and were recognized at the Award Ceremony and Opening Reception on Monday, February 4 at 5:15 PM in the Regency Foyer:

Rhea Ashmead, University of Victoria, Victoria, Canada
Hojun Choi, Korea Advanced Institute of Science and Technology (KAIST), Daedeok Innopolis, Daejeon, South Korea
Chloe Christensen, University of Victoria, Victoria, Canada
Jenny Do, National Institutes of Health (NIH), Bethesda, Maryland, USA
Areian Eghbali, National Institutes of Health (NIH), Bethesda, Maryland, USA
Eric Joshua Garcia, National Institutes of Health (NIH), Bethesda, Maryland, USA
Francyne Kubaski, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
Murtaza Nagree, University of Toronto, Toronto, Canada
Yanyan Peng, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Hiroyuki Yamakawa, Keio University School of Medicine, Tokyo, Japan

Danilo A. Tagle, PhD, MS received the 2019 Roscoe O. Brady Award for Innovation and Accomplishment

Danilo A. Tagle, PhD, MS, is associate director for special initiatives at NCATS. He also recently served as acting director of the NCATS Office of Grants Management and Scientific Review and currently serves as executive secretary to the NCATS Advisory Council and Cures Acceleration Network Review Board. Prior to NCATS, Tagle was a program director for neurogenetics at the National Institute of Neurological Disorders and Stroke (NINDS), where he was involved in developing programs concerning genomics-based approaches for basic and translational research in inherited brain disorders.

Prior to joining NINDS in 2001, Tagle was an investigator and section head of molecular neurogenetics at the National Human Genome Research Institute and has been involved in the highly collaborative effort toward the positional cloning of genes for Huntington’s disease, ataxia-telangiectasia and Niemann-Pick disease type C. He has served on numerous committees and advisory boards, including the editorial boards of the journals Gene and the International Journal of Biotechnology.

Tagle leverages key resources and expertise through partnerships with stakeholders in biomedical research, including various government agencies, nonprofits, patient advocacy groups, industry organizations, pharmaceutical corporations and others in the private sector. He leads and provides scientific and programmatic oversight and coordination to the following trans-NIH programs:

Extracellular RNA Communication
NIH Microphysiological Systems (also known as the Tissue Chip for Drug Screening program)
Regulatory Science
Stimulating Peripheral Activity to Relieve Conditions (SPARC)

Tagle obtained his PhD in molecular biology and genetics from Wayne State University School of Medicine in 1990. He was an NIH National Research Service Award postdoctoral fellow in human genetics in the laboratory of Francis S. Collins, MD, PhD, at the University of Michigan. Tagle has authored more than 150 scientific publications and has garnered numerous awards and patents.

Dr. Tagle received the 2019 WORLDSymposium Roscoe O. Brady Award for Innovation and Accomplishment on Tuesday, February 5, 2019 at 7:30 AM.

2019 Poster Sessions

WORLDSymposium™ 2019 abstract submission site opened July 1, 2018 and closed October 1, 2018.

Click here to download the 2019 poster list.

If a poster number is not listed, it means the first author of the abstract chose not to present a poster at WORLDSymposium 2019.

Over 440 abstracts were presented at the two WORLDSymposium poster sessions. These sessions are an excellent opportunity to see, hear and discuss specific research topics directly with the abstract authors, as well as enjoy hors d’oeuvres and a cash bar with colleagues from around the globe.

All abstracts received by the October 1, 2018 deadline were considered for platform presentation and inclusion in the lysosomes issue of Molecular Genetics and Metabolism (MGM) which will be published in February 2019. Poster notifications and assigned poster numbers were sent to the first author of the submitted abstract at the beginning of December, 2018.

Late-breaking abstract submission (for poster consideration only) opened on November 1 and closed on December 1, 2018. Accepted late-breaking abstracts will not be published in the February 2019 “Lysosomes Issue” of Molecular Genetics and Metabolism.

Registered attendees will receive an electronic copy of the program and abstracts when they check in at the WORLDSymposium 2019 registration desk. The program and abstracts become copyrighted and will be available to non-registrants through Elsevier.

It is the policy of WORLDSymposium to publish all abstracts with the list of authors exactly as the abstract was submitted to WORLDSymposium. The first author of the submitted abstract was listed as the presenting author on the Preliminary Program, Agenda, and Poster List.

2019 Posters Sessions

Poster receptions were scheduled on Tuesday, February 5, 2019 and Wednesday, February 6, 2019 from 4:30 – 6:30 PM.

Poster presenters with a last name starting with A-L (First Author Last Name) presented their posters on Tuesday, February 5, 2019, from 4:30-6:30 PM.

Poster presenters with a last name starting with M-Z (First Author Last Name) presented their posters on Wednesday, February 6, 2019, from 4:30-6:30 PM.

All late-breaking abstracts were assigned to the poster session on Wednesday, February 6, 2019, from 4:30-6:30 PM.

Poster presenters were required to be in attendance at their poster for their assigned timeframe. The poster sessions provide an excellent opportunity to discuss concepts, share knowledge, and exchange ideas with abstract authors and other WORLDSymposium participants.

Mark Dant received the 2019 Patient Advocate Leader (PAL) Award

Each year, WORLDSymposium recognizes one individual for patient advocacy leadership in the field of lysosomal disease. The 2019 Patient Advocate Leader (PAL) award was presented to Mark Dant, the current Chairman of the Board of the Washington DC-based EveryLife Foundation for Rare Diseases, a science-based advocacy organization dedicated to accelerating biotech innovations for rare disease treatments through science-driven public policy. Mark is also the founder and Volunteer Executive Director of the Ryan Foundation and former President and CEO of the National MPS Society.

In 1992, while working as a police officer in the Dallas area, Mark and his wife Jeanne founded The Ryan Foundation with a bake sale after their only child, three-year old Ryan was diagnosed with MPS I. At that time, life expectancy for children with MPS I was less than 15 years. Mark began an immediate global search for scientists and philanthropists who might aid in finding a treatment in time to help children and families living with MPS realize the promise of tomorrow. A conversation with a research scientist at a symposium in Dusseldorf Germany eventually led Mark to Dr. Emil Kakkis, a young researcher at UCLA who was working on a project to help treat MPS, but had little funding. The Ryan Foundation partnered with Dr. Kakkis and provided key funding for his project, which culminated in the development of laronidase, the first and only drug currently approved to treat MPS I. Ryan, now 30 and a graduate of the University of Louisville, is the longest treated person in the world with MPS I. Since the bake sale, the Ryan Foundation has funded millions of dollars in rare disease research.

For the past 25+ years, Mark and the Ryan Foundation have partnered with numerous research scientists and universities to help innovative projects move toward treatment in lysosomal storage disease; to include the essential published laboratory work which provided proof of concept for Intrathecal Enzyme delivery in lysosomal storage disease. Mark and his family have been key advocates speaking to the FDA and in 2009 successfully championed the US House of Representatives to pass the Ryan Dant Health Care Opportunity Act, a bill designed to help those living on Medicaid assistance become gainfully employed. The Dant’s journey has been documented on CBS 60 Minutes, CNN, Biography Magazine, Readers Digest in 13 languages around the world, Golf Digest, the LA Times and numerous newspapers and news outlets across the US.

Mark retired from police work in 2016 as Assistant Chief of Police after serving 32 years as a Patrol Officer, Detective, and Commander leading multiple divisions and Bureaus to include Patrol, Criminal Investigations, Intel, and SWAT. Mark spends his time now volunteering for the EveryLife Foundation, the Ryan Foundation, and numerous other rare disease organizations to help empower the patient advocate through the understanding that all of us have the power to turn action to hope and hope to reality. Mark’s message is that it is not the entity, but the individual who holds the responsibility to make true change.

On Wednesday, February 6, 2019 at 7:30 AM, Mark was presented with the WORLDSymposium 2019 Patient Advocate Leader Award.

Chester B. Whitley, PhD, MD Delivered Keynote Address on Wednesday, February 12, 2019

WORLDSymposium was pleased to announce Chester (Chet) B. Whitley, Ph.D., M.D., as the Keynote Speaker for Thursday, February 7, 2019. Dr. Whitley is a tenured Professor in the Department of Pediatrics, the Department of Experimental and Clinical Pharmacology, and Director of the Advanced Therapies Program at the University of Minnesota.

In 1983, Dr. Whitley conducted the first U.S. trials of bone marrow transplantation for Hurler syndrome, other mucopolysaccharidoses, and selected lysosomal diseases including Krabbe disease, Tay-Sachs disease. With the first transplant for Hurler syndrome in the U.S.A. (September 13, 1983, University of Minnesota)¹ and the continuing clinical trials during the next decade,² he characterized the level of response and clinical outcomes. In the case of Hurler syndrome, cognitive testing and imaging showed protection of the brain despite the seemingly impenetrable blood-brain barrier. Being the very first efficacious treatment for a lysosomal disease, this procedure of hematopoietic stem transplant provided the proof-of-principle for development of future enzyme replacement therapies, gene therapy, and other systemic treatments. During these early transplant studies, Dr. Whitley expanded upon the 1960’s “cross-correction” observations at NIH in cultured fibroblasts, and coined the term “metabolic cross-correction”1 and characterized multiple different mechanisms accounting for the clinical responses in patients. In conversation with the U.S.F.D.A. in the early 1990’s, he coined the term “ultra-orphan disease” to differentiate those conditions that are orders of magnitude more rare than the legislated definition of “orphan disease” with prevalence of <200,000.

Dr. Whitley directs the CLIA-certified Gene Therapy and Diagnostics Lab, the first laboratory in North America to offer complete sequencing of a gene to be offered as a ‘clinical diagnostic’ (non-research) test.

In the late 1990s, Dr. Whitley conducted the first clinical trial of gene therapy for a mucopolysaccharidosis condition, Hunter syndrome.³ At that time, he invented⁴ the DMB dye-binding test for measuring urine glycosaminoglycans (GAG), the most common method for quantifying GAG in diagnostic laboratories globally.

He is also responsible for a number of other ‘firsts’: (a) discovering a ‘pseudo-deficiency’ allele for MPS^5,6; (b) finding that combining therapies, e.g., enzyme replacement therapy (ERT) after bone marrow transplantation⁷ may enhance metabolic correction; (c) demonstrating that small amounts of intravenous laronidase enzyme cross the blood-brain barrier and reduces the pathology in the brain, and improves the learning of mice with Hurler syndrome⁸; and, recently, that (d) intravenous zinc-finger nuclease gene-editing prevents brain disease in mice with Hurler syndrome⁹ and Hunter syndrome¹⁰.

Dr. Whitley conceived and organized the 1st International Symposium on Mucopolysaccharidosis and Related Diseases (May 20-23, 1988, Minneapolis, Minnesota).¹¹ He is also Director of the Gene Therapy Center at the University of Minnesota supported by an NIH program project grant Gene Therapy for Metabolic Disease for two decades (5P01HD032652).

He is the founding Principal Investigator of the NIH-funded Lysosomal Disease Network currently coordinating 21 clinical studies at 18 institutions. Dr. Whitley is the founding organizer (May 12-15, 2004, Minneapolis, MN USA) and current Course Director of the annual We’re Organizing Research on Lysosomal Diseases scientific meeting ‘WORLDSymposia’ an international forum that fuses basic, translational and clinical research on lysosomal diseases.

On Thursday, February 7, 2019, at 7:30 AM, Dr. Whitley’s Keynote Address The ‘New’ Lysosomal Disease Network, described how the intersection of past lysosomal disease research and current, ongoing, unmet need, has created both the springboard for the next generations of therapies, and provided the overarching vision for researchers and clinicians in the LDN going forward.

Whitley CB, Ramsay NKC, Kersey JH, Krivit W: Bone marrow transplantation for Hurler syndrome. Assessment of metabolic correction. Birth Defects 22:7-24, 1986.
Whitley CB, Belani K, Chang PN, Summers CG, Blazar BR, Tsai MY, Latchaw RE, Ramsay NKC, Kersey JH: Long-term outcome of Hurler syndrome following bone marrow transplantation, Am J Med Genet 46:209-218, 1993.
U.S. Food and Drug Administration BB-IND: #5370; Autologous Peripheral Blood Stem Cells Cultured Ex-Vivo with Anti-CD3 (OKT3, Ortho) and Interleukin-2 (Chiron); Transduced (L2SN, University of Minnesota) Expressing IDS Gene; approved to initiate clinical trial (June, 1995). Active clinical trial period: – January 10, 1998.
NIH Recombinant DNA Advisory Committee application; Retroviral-Mediated Transfer of the Iduronate-2-Sulfatase Gene Into Lymphocytes for Treatment of Mild Hunter Syndrome (Mucopolysaccharidosis Type II), Human Gene Therapy Protocol, University of Minnesota Medical School, Minneapolis, MN, Chester B. Whitley, Ph.D., M.D., R. Scott McIvor, Ph.D., Susan A. Berry, M.D., Bruce R. Blazar, M.D., John H. Kersey, M.D., Richard A. King, M.D., Ph.D., Anthony J. Faras, Ph.D., Richard E. Latchaw, M.D., Jeffrey J. McCullough, M.D.,
Norma K.C. Ramsay, M.D.
Method for the Detection of Mucopolysaccharide Disease (Serial No. 194,553) submitted May 13, 1988; continuation-in-part (Serial No. 07/297,051) submitted January 16, 1989; amendment, Method for the detection of mucopolysaccharide storage disease, continuation-in-part (Serial No. 07/297,051) submitted May 29, 1991; patent allowed, November, 1993; patent application (Serial No. 07/806,833) Method for the Detection of Mucopolysaccharide Storage Diseases issued on May 10, 1994 as U.S. Patent No. 5,310,646.
Whitley CB, Gorlin RJ, Krivit W. A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome. Am J Med Genet 28(1). 1987. 233-243. PMID: 3118714.
Aronovich EL, Pan D, Whitley CB, Molecular genetic defect underlying alpha-L-iduronidase pseud
odeficiency. Am J Hum Genet. 1996 Jan;58(1):75-85. PMCID: PMC1914939.
Whitley CB, Utz JR. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): a single dose of galsulfase further reduces urine glycosaminoglycans after hematopoietic stem cell transplantation. Mol Genet Metab 101(4). 2010. 346-348. PMID: 20800524.
Ou, L., DeKelver R.C., Rohde M., Tom S., Radeke R., St. Martin S., Santiago,Y, Sproul S., Przybilla M.J., Koniar B.L., Podetz-Pedersen K.M., Laoharawee K., Cooksley R.D., Meyer K.E., Holmes M.C., McIvor R.S., Wechsler T., Whitley C.B. ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome, Molecular Therapy (2018), doi: https://doi.org/10.1016/j.ymthe.2018.10.018.
Ou, L., DeKelver R.C., Rohde M., Tom S., Radeke R., St. Martin S., Santiago,Y, Sproul S., Przybilla M.J., Koniar B.L., Podetz-Pedersen K.M., Laoharawee K., Cooksley R.D., Meyer K.E., Holmes M.C., McIvor R.S., Wechsler T., Whitley C.B. ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome, Molecular Therapy (2018), doi: https://doi.org/10.1016/j.ymthe.2018.10.018.
K. Laoharawee, R. DeKelver, K. Podetz-Pedersen, M. Rohde, S. Sproul, H. Nguyen, T. Nguyen, S.S. Martin, L. Ou, S. Tom, C.B. Whitley, R.S. McIvor. Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-mediated In Vivo Genome Editing. Molecular Therapy 26(4):1127-1136, April 2018. doi.org/10.1016/j.ymthe.2018.03.002
Whitley, CB, J.M. Opitz, J.F. Reynolds. First International Congress on Mucopolysaccharidosis and Related Diseases ‐ 70 Years of Research, University of Minnesota, Minneapolis, May 20–23, 1988. Am J Med Genet 32(2) 1989. doi.org/10.1002/ajmg.1320320233

2020 WORLDSymposium Young Investigator Awards Announced

Congratulations to the eleven individuals selected who received the WORLDSymposium Young Investigator Award for 2020. The award was a partial scholarship towards attendance at WORLDSymposium 2020. Numerous individuals submitted an application for the award, and the review process was difficult due to the excellent caliber of all the applicants.

WORLDSymposium would like to congratulate all of the applicants for their hard work. The following individuals received the WORLDSymposium Young Investigator Award for 2020 at the start of the Scientific Meeting on Monday, February 10, 2020 at 1:00 PM in the General Session (Regency Ballroom R):

Joao B. Augusto, University College London, London, United Kingdom
Nicholas Bascou, University Pittsburgh Medical Center (UPMC), Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
Nuthana Prathivadi Bhayankaram, Royal Manchester Children’s Hospital, Manchester, United Kingdom
Poulomee Bose, Centre Hospitalier Universitaire, Sainte-Justine (CHU St. Justine), Montreal, Quebec, Canada
Eric Joshua Garcia, National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA
Mohammad A. Hossain, Jikei University School of Medicine, Tokyo, Japan
Jeffrey Y. Huang, Children’s Hospital of Orange County (CHOC), Orange, California, USA
Sarah Kim, University of Minnesota, Minneapolis, Minnesota, USA
Chelsie Poffenberger, National Institutes of Health (NIH), Bethesda, Maryland, USA
Michael Przybilla, University of Minnesota, Minneapolis, Minnesota, USA
Weihua Tian, University of Copenhagen, Copenhagen, Denmark

2020 PATIENT ADVOCATE SHOWCASE

Batten Disease Support and Research Association

BDSRA is dedicated to funding research for treatments and cures, providing family support services, advancing education, raising awareness, and advocating for legislative action. BDSRA is now the largest support and research organization dedicated to Batten disease in North America.

Cure Sanfilippo Foundation

Cure Sanfilippo Foundation is a 501c3 nonprofit whose mission is to advocate for and fund research directed towards a cure or treatment options for children with Sanfilippo Syndrome, a rapidly degenerative and terminal disease, currently with no cure or treatment.

European Working Group on Gaucher Disease

The aim of the EWGGD is to promote clinical and basic research into Gaucher disease for the ultimate purpose of improving the lives of patients with this disease; it brings together clinicians, scientists and patients in an open forum for discussion on all aspects of the condition. The EWGGD invites worldwide medical and academic groups working in the Gaucher field to join us. Please visit our booth/website for registration details.

EveryLife Foundation for Rare Diseases

The EveryLife Foundation for Rare Diseases is dedicated to accelerating biotech innovation for rare disease treatments through science-driven public policy. We can do more with the science we already have and bring life-saving treatments to millions of people suffering from rare diseases.

Fabry International Network

The primary aim of The Fabry International Network (FIN) is to facilitate collaboration between Patient Organisations to support those affected by Fabry Disease. It seeks to do this primarily through enabling communication, promoting good practices and acting as an independent forum for Fabry Associations. FIN is connected to over 45 countries around the world. Membership is free and open to any National Patient Organisation in which Fabry patients are represented. In difficult to reach geographical areas, FIN relies on individual supporters, such as Mr Martynas Davidonis from Lithuania to help FIN reach Eastern European Patient Organisations or Mr Wanderlei Cento Fanta, the founder and president of Abraff in Brazil, helping FIN with South America’ s Associations. FINs Vision is of a world where every single person affected by Fabry disease has the best quality of life possible through early diagnosis, treatment and cure.

Global Genes

Global Genes® is a leading rare disease patient advocacy organization. Our mission is to create a globally connected community equipped to eliminate the challenges of rare disease. We achieve this through connecting, empowering and inspiring the rare disease community.

MLD Foundation

We C.A.R.E.™ – Compassion, Awareness, Research & Education for metachromatic leukodystrophy (MLD). Global footprint. Support for families, especially newly diagnosed. Very active in Rare Disease policy & awareness, and newborn screening at federal, state & global levels. Actively working on an identified MLD newborn screen pilot.

MSD Action Foundation

Our goal is to promote and support research that will lead to positive clinical outcomes and quality of life for patients suffering from Multiple Sulfatase Deficiency.

National Fabry Disease Foundation

The National Fabry Disease Foundation is a nonprofit charitable organization with many valuable programs to provide disease education and to provide support and assistance to families with Fabry disease. They strive to improve disease understanding, diagnoses, and management and to enable individuals with Fabry to live better and longer lives.

National MPS Society

The National MPS Society exists to find cures for MPS and ML. We provide hope and support for affected individuals and their families through research, advocacy and awareness of these devastating diseases.

Salla Treatment and Research Foundation

Promoting research, education, and family support as we pursue treatments for Salla Disease.

United MSD Foundation

The United MSD Foundation advocates for, supports, and funds biomedical research to cure Multiple Sulfatase Deficiency (MSD) and avails its research to cure other lysosomal storage diseases.

2020 EXHIBITORS

Amicus Therapeutics, Inc.

Amicus Therapeutics is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare metabolic diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a robust pipeline of cutting-edge, first- or best-in-class medicines for rare metabolic diseases.

ARCHIMEDlife

ARCHIMEDlife is an innovative and dynamic Medical Laboratory providing high quality, specialized diagnostic services for Rare Diseases, located in Vienna, Austria. The company is committed to helping physicians and their patients avoid diagnostic odysseys by delivering leading-edge, rapid services. More than 20,000 physicians in 75 countries have trusted in ARCHIMEDlife.

Audentes Therapeutics

Audentes Therapeutics is a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases. We are leveraging our AAV gene therapy technology platform and proprietary manufacturing expertise to develop programs across three modalities: gene replacement, vectorized exon skipping, and vectorized RNA knockdown. Our product candidates are showing promising therapeutic profiles in clinical and preclinical studies across a range of neuromuscular diseases. Audentes is a focused, experienced and passionate team driven by the goal of improving the lives of patients.

Baebies

We believe “everyone deserves a healthy start”. Baebies develops products that enable early disease detection for children including: SEEKER®, an FDA-cleared and CE-marked newborn screening platform for lysosomal storage disorders (Pompe, MPS I, Gaucher, Fabry), and FINDER, a CE-marked low volume pediatric testing platform, not commercially available in the U.S.

BioMarin Pharmaceutical

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. Approved products include the first and only therapies for PKU, LEMS, MPS I, MPS VI, MPS IVA, and CLN2 disease. Clinical development programs include investigational therapies for Hemophilia A, Achondroplasia, MPS IIIB, Friedreich’s Ataxia and other rare diseases.

Blueprint Genetics

Blueprint Genetics is a genetic testing company, providing single genes, panels and whole exome sequencing by next generation sequencing. This year, Blueprint Genetics is expanding these services by offering biochemical testing to better collaborate with clinicians, researchers and personalized health care companies to provide patients with a faster, earlier diagnoses.

CENTOGENE US LLC

CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients. We are focused on bringing rationality to treatment decisions and accelerating the development of new orphan drugs by using our knowledge of the global rare disease market, including its epidemiological and clinical heterogeneity, and our innovative biomarkers. Our data repository includes epidemiologic, phenotypic, and genetic information from over 450,000 patients sourced from over 115 countries thus reflecting the genetic differences in global ethnicities. We believe this represents the only platform that comprehensively analyzes multilevel data to improve the understanding of rare diseases, which can aid in the identification of patients and improve our pharmaceutical partners’ ability to bring orphan drugs to the market. As one of the largest rare disease companies worldwide, CENTOGENE is dedicated to transforming the science of genetic information into solutions and hope for patients with rare diseases and their families.

Charles River

Discovery from Charles River is the CRO of choice with a proven track record of successful drug development in neurodegenerative rare diseases. Offering scientific excellence and integrated services that take clients from hit ID to IND, our client-focused collaborative team works with clients to find and follow the optimum path to market.

Chiesi Farmaceutici S.p.A.

Based in Parma, Italy, Chiesi Farmaceutici is an international research-oriented group with over 85 years’ experience in the pharmaceutical sector, and is present in 28 countries. The group researches, develops and commercialises innovative medicines in the respiratory disease, special care and rare disease therapeutic areas. The Group’s Research & Development centre is based in Parma (Italy) and integrated with 6 other important research and development groups in France, the USA, the UK, Sweden and Denmark, to promote its pre-clinical, clinical and registration programmes. The Group employs around 5,700 people.

Denali Therapeutics

Lysosomal Storage Disease with neurocognitive dysfunction represents a major medical challenge. Denali Therapeutics is dedicated to defeating neurodegenerative diseases through rigorous therapeutic discovery and development. Our scientific strategy is guided by three overarching principles: 1) Genetic pathway potential: selection of targets with a genetic link to disease; 2) Engineering brain delivery: specifically designing therapeutics to cross the blood-brain barrier; and 3) Biomarker-driven clinical development: clinical development is enabled by biomarkers to monitor early effects of the drug and select the right patients and the right dose. We believe that the application of these principles will significantly increase our probability of success and will accelerate the timing to bring effective therapeutics to patients.

Enzyvant

Enzyvant is a biopharmaceutical company focused on developing innovative treatments for patients with rare diseases. Enzyvant has initiated a rolling BLA submission with the FDA for RVT-802, an investigational tissue-based therapy for the treatment of primary immunodeficiency associated with complete DiGeorge Anomaly. Enzyvant is simultaneously initiating a clinical trial of RVT-801, an investigational enzyme replacement therapy for the treatment of Farber disease. Enzyvant plans to develop treatments for additional rare diseases with high unmet need.

European GD Network

Our international team of GD experts are researching the quality of care provided to GD patients by hematologists around the globe. This research will improve clinical management by developing and implementing a set of minimum consistent core outcomes to improve both future GD clinical guidelines and future GD clinical trials.

Greenwood Genetic Center

The Greenwood Genetic Center is a nonprofit institute organized to provide clinical genetic services, diagnostic laboratory testing, educational programs and resources and research in the field of medical genetics. Our laboratory offers biochemical, cytogenetic, and molecular testing.

Homology Medicines, Inc.

Homology Medicines is based on an important scientific discovery – a novel set of adeno-associated virus vectors derived from human hematopoietic stem cells (AAVHSCs) that are designed to precisely and efficiently deliver genetic medicines in vivo either through gene therapy or by harnessing the body’s natural DNA repair process of homologous recombination through nuclease-free gene editing.

Our technology platform offers substantial benefits over current gene editing and gene therapy approaches and could potentially enable the development of one-time curative treatments.

Idorsia Pharmaceutical

The purpose of Idorsia is to discover, develop and bring more, innovative medicines to patients.

Invitae

Invitae’s mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. Our goal is to aggregate most of the world’s genetic tests into a single service with higher quality, faster turnaround time and lower prices.

JCR Pharmaceuticals Co., Ltd.

JCR Pharmaceuticals has been engaged in the R&D of pharmaceuticals for rare diseases ever since its inception. Its philosophy; “Contributing towards people’s healthcare through pharmaceutical products” drives us to leverage our biotechnology expertise, cell therapy and gene therapy technologies and regenerative medicine to develop treatment options for under-served patient communities.

Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)

LDTRC is a non-profit organization focused on the individual patients with Lysosomal and other rare disorders. LDRTC offers clinical care by the highest standards with a special expertise in translational medicine, and conducts investigator initiated studies, bench-to-bedside studies, self sponsored multi-center collaborative trials, pilot and proof-of-concept studies.

Neurogene Inc.

Neurogene is accelerating development of new genetic medicines to people with devastating neurological diseases and their families.

Orchard Therapeutics

Orchard Therapeutics transforms the lives of patients with rare diseases through innovative gene therapies.

Orphazyme

Orphazyme is biopharmaceutical company focused on the development of treatments for serious, progressive neurological or neuromuscular diseases. Arimoclomol, a heat shock protein amplifier that restores protein homeostasis, is in development for Neiman-Pick disease type C (NPC), Gaucher disease, Amyotrophic Lateral Sclerosis (ALS), and sporadic Inclusion Body Myositis (sIBM).

Patient Discovery

Patient Discovery is changing the way patients with complex conditions are understood, supported and treated. Patient Pathfinder Platform brings together the needs of patients, providers, foundations and industry to solve common problems for complex conditions. Patient Pathfinder allows patients to search for treatment centers, clinical trials and prepare for appointments.

Pfizer, Inc.

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time.

PROMETRIKA, LLC

PROMETRIKA is a full-service clinical research organization (CRO) offering our rare-disease focused clients extensive expertise in monitoring, biostatistics, data management, medical writing, safety, and regulatory submission services. The PROMETRIKA team has a long history of working together, including hundreds of clinical trials, extensive FDA interaction and several successful NDA submissions.

Protalix Ltd.

Protalix is dedicated to discovering, developing, and marketing recombinant therapeutic proteins with potentially improved clinical profiles, produced with our ProCellEx® plant cell-based protein expression platform. Our first approved product was taliglicerase alfa for Gaucher disease. Our pipeline includes pegunigalsidase alfa, a novel enzyme replacement therapy in phase III studies for the treatment of Fabry disease and other investigational products in clinical development for inflammatory bowel disease and cystic fibrosis.

QPS Austria GmbH

QPS Austria is a leading CRO for CNS drug discovery and development. The preclinical department routinely performs studies using in vitro and in vivo models for lysosomal storage and neurodegenerative diseases. Models are evaluated by behavioral, histological and biochemical readouts. The clinical department performs clinical studies of different phases.

Rare Disease Research

Rare Disease Research is an independent company that strives to provide access to investigational treatments for pediatric and adult patients with rare conditions that otherwise would not have the opportunity to participate in cutting-edge clinical research efforts. We partner with physicians, industry, and academic institutions. We believe everyone deserves access.

Retrophin, Inc.

Retrophin is a biopharmaceutical company dedicated to identifying, developing and delivering life-changing therapies to people living with rare disease.

Sanofi Genzyme

Sanofi Genzyme, the specialty care global business unit of Sanofi, focuses on rare diseases, rare blood disorders, multiple sclerosis, oncology, and immunology. We help people with debilitating and complex conditions that are often difficult to diagnose and treat. Our approach is shaped by our experience developing highly specialized treatments and forging close relationships with physician and patient communities. We are dedicated to discovering and advancing new therapies, providing hope to patients and their families around the world.

Sigilon Therapeutics

Sigilon Therapeutics is developing functional cures for chronic diseases through its Shielded Living Therapeutics™ platform. The platform includes human cells engineered to produce the crucial proteins needed by patients living with diseases such as LSDs. The cells are protected by Sigilon’s Afibromer™ biomaterials matrix, which shields them from immune rejection.

Spark Therapeutics

At Spark Therapeutics, we are committed to developing potential gene therapies for serious genetic diseases and bringing those investigational therapies to patients. One of our areas of research is Pompe disease, a lysosomal storage disorder and neuromuscular disease resulting from a mutation in the acid alpha-glucosidase (GAA) gene. Our founders and members of our scientific team have devoted decades to the research of gene therapies with the goal of making these investigational, potential one-time treatments a reality.

Takeda Pharmaceuticals

Shire is now part of Takeda. Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. We focus R&D efforts on four therapeutic areas: Oncology, Gastroenterology, Neuroscience and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines.

Ultragenyx Pharmaceutical

Ultragenyx is a biopharmaceutical company committed to bringing to market novel products for the treatment of rare and ultra-rare diseases, with a focus on serious, debilitating genetic diseases. The Company has rapidly built and advanced a diverse portfolio of product candidates with the potential to address diseases for which the unmet medical need is high, the biology for treatment is clear, and for which there are no approved therapies.

2020 Satellite Symposia Schedule

Tuesday Breakfast, February 11, 2020, 6:15 – 7:15 AM
Gaucher and ASMD. Understanding Differences and Similarities in Disease Mechanisms
Supported by Sanofi Genzyme.

Tuesday Breakfast, February 11, 2020, 6:15 – 7:15 AM
Genetics: Early diagnosis and driving precision medicine in pediatric neurology.
Long-term treatment with Brineura® (cerliponase alfa)
Supported by BioMarin Pharmaceutical, Inc.

Tuesday Lunch, February 11, 2020, 11:45 AM – 12:45 PM
Gaucher disease: Can we build a better roadmap for patient care?
CME Satellite Symposium.
Accredited provider: University of Louisville School of Medicine.
Supported by an educational grant from Takeda.

Tuesday Lunch, February 11, 2020, 11:45 AM – 12:45 PM
Cardiovascular Implications in Fabry Disease:
A multidisciplinary approach to diagnosis, assessment and treatment
CME Satellite Symposium.
Accredited provider: Postgraduate Institute for Medicine.
Supported by an independent educational grant from Amicus Therapeutics Inc.

Tuesday Dinner, February 11, 2020, 6:30 – 8:30 PM
Lysosomal Disorders: Lentiviral gene therapy and the promise of freedom for life
Supported by AVROBIO, Inc.

Tuesday Dinner, February 11, 2020, 6:30 – 8:30 PM
Unveiling ASMD: A closer look into disease diagnosis and burden
Supported by Sanofi Genzyme.

Wednesday Breakfast, February 12, 2020, 6:15 – 7:15 AM
MPS Treatment and Landscape Update
Supported by Ultragenyx Pharmaceutical Inc.

Wednesday Breakfast, February 12, 2020, 6:15 – 7:15 AM
Emerging Developments in the Management of Metachromatic Leukodystrophy
Supported by Orchard Therapeutics.

Wednesday Lunch, February 12, 2020, 11:45 AM – 12:45 PM
Respiratory Involvement in Pompe Disease
Supported by Sanofi Genzyme.

Wednesday Lunch, February 12, 2020, 11:45 AM – 12:45 PM
Fabry Disease: Translating Pharmacogenetics into Clinical Practice
Supported by Amicus Therapeutics Inc.
This satellite is open only to registered attendees from outside the United States. International participants only.

Wednesday Dinner, February 12, 2020, 6:30 – 8:30 PM
Pivotal Trials, Comparative Studies and Clinically Relevant Outcomes in Fabry Disease
Supported by Sanofi Genzyme.
This satellite is open only to registered attendees from outside the United States. International participants only.

Thursday Breakfast, February 13, 2020, 6:15 – 7:15 AM
New Insights on MPS I Genotype-Phenotype Relationships in the Era of Newborn Screening
Supported by Sanofi Genzyme.

Thursday Breakfast, February 13, 2020, 6:15 – 7:15 AM
Fabry Disease Management: 2020 and Beyond
CME Satellite Symposium.
Accredited provider: Postgraduate Institute for Medicine.
Supported by an independent educational grant from Chiesi USA, Inc.

Thursday Lunch, February 13, 2020, 11:45 AM – 12:45 PM
Neurodegenerative Consequences in Lysosomal Diseases: Peripheral, Central and Autonomic
Supported by Takeda.

Thursday Lunch, February 13, 2020, 11:45 AM – 12:45 PM
Fabry in Females: Physician and Patient Insights
Supported by Sanofi Genzyme.

These Satellite Symposia were not part of the official WORLDSymposium™ program, and WORLDSymposium did not approve or endorse any commercial products or services discussed during the Satellite Symposia or offered for sale by any corporate supporter of the Satellite Symposia. These symposia may or may not offer CME credits; these sessions were not approved for CME through WORLDSymposium.

Registration for the 16th Annual Scientific Meeting and an official WORLDSymposium name badge were required to attend any of the satellite symposia.

2020 Emerging Trends in Lysosomal Biology & Lysosomal Diseases: State-of-the-art for Experts

Monday, February 10, 2020 from 8:00 – 11:30 AM

For the eighth consecutive year, WORLDSymposium™ began with “Emerging Trends” on Monday morning, February 10, 2020 at 8:00 AM. This 3.5-hour CME/CE course provided a state-of-the-art update for experts working in lysosomal biology and lysosomal diseases. This course was a summary of the latest research trends and other advances in the field.

The content provided comprehensive information on lysosomal diseases, but does not overlap or replace the scientific data being presented during WORLDSymposium2020. Registration Required.

Learning Objectives

Upon completion of this educational activity, the participant should be better able to:

Describe the basic structure, function and molecular biology of lysosomes.
Identify specific lysosomal diseases, their clinical manifestations, and means of diagnosis.
Review current treatments for lysosomal diseases, the potential side effects, and their expected clinical outcomes.
Correlate the molecular biology of lysosomes with clinical features, diagnostic testing, and treatment approaches.

Preliminary Agenda

8:00 AM
Introduction and Overview of Course
Chester B. Whitley, PhD, MD

8:10 AM
Lysosomal Disease Phenotypes
Chester B. Whitley, PhD, MD

8:30 AM
Lysosomal Function and Pathogenesis
Steven U. Walkley, DVM, PhD

9:00 AM
Remarkable Cases I
Marc C. Patterson, MD

9:30 AM
Break

9:45 AM
Current Treatments for Lysosomal Diseases
Jeanine R. Jarnes, PharmD

10:05 AM
Newborn Screening
Amy Gaviglio, MS, LCGC

10:25 AM
Future Treatments for Lysosomal Diseases
Jeanine R. Jarnes, PharmD

10:45 AM
Remarkable Cases II
Marc C. Patterson, MD

11:05 AM
Patient Advocate’s Perspective on Experimental Therapies
Cara O’Neill, MD

11:25 AM
Closing Remarks
Chester B. Whitley, PhD, MD

11:30 AM
Adjourn

Invited Faculty

Jeanine R. Jarnes, PharmD, BCOP, BCPS
Adjunct Assistant Professor, Experimental and Clinical Pharmacology
College of Pharmacy
University of Minnesota, Fairview
Minneapolis, MN, USA

Amy Gaviglio, MS, LCGC
G2S Corporation
Newborn Screening and Molecular Biology Branch
Division of Laboratory Sciences, NCEH
Centers for Disease Control and Prevention
Minneapolis, MN

Cara O’Neill, MD
Chief Science Officer
Cure Sanfilippo Foundation
Pediatrician
Columbia, SC

2020 Poster Session Abstracts

WORLDSymposium™ 2020 featured over 480 scientific abstracts presented at three separate poster sessions. These sessions were an excellent opportunity to see, hear and discuss specific research topics directly with the abstract authors, as well as enjoy hors d’oeuvres and a cash bar with colleagues from around the globe.

Click here to download the 2020 poster list.

If a poster number is not listed, it means the first author of the abstract chose not to present a poster at WORLDSymposium 2020.

All abstracts received by the October 1, 2019 deadline were considered for platform presentation and inclusion in the lysosomes issue of Molecular Genetics and Metabolism (MGM) which was published in February 2020. Poster notifications and assigned poster numbers were sent to the first author of the submitted abstract at the beginning of December, 2019.

Late-breaking abstract submission (for poster consideration only) opened on November 1 and closed on December 1, 2019. Accepted late-breaking abstracts were not published in the February 2020 “Lysosomes Issue” of Molecular Genetics and Metabolism but was published in the WORLDSymposium program materials onsite.

Registered attendees had access to an electronic copy of the program and abstracts via the WORLDSymposium 2020 Mobile App. Registered attendees logged onto the Mobile App using the confirmation code they received with their invitation to the Mobile App. The program and abstracts are copyrighted and was available to non-registrants through Elsevier.

It is the policy of WORLDSymposium to publish all abstracts with the list of authors exactly as the abstract were submitted to WORLDSymposium. The first author of the submitted abstract was listed as the presenting author on the Preliminary Program, Agenda, and Poster List.

2020: Posters were Divided into Three (3) Separate Sessions

Poster receptions were scheduled from 4:30-6:30 PM on:

Monday, February 10, 2020
Tuesday, February 11, 2020 and
Wednesday, February 12, 2020

All posters were mounted beginning at 9:30 AM on the assigned presentation date, but no later than 4:00 PM on the day the abstract is scheduled to be presented. All posters must be taken down at 6:30 PM the same day after being presented. New abstracts were presented each day.

Poster presenters were assigned a Presentation Number and assigned to a specific date and time. Due to space limitations, each poster was only presented on the assigned date. The date and time assigned were communicated to the first author of the abstract.

Abstracts numbered 1-164 were presented on Monday, February 10, 2020.
Abstracts numbered 165-328 were presented on Tuesday, February 11, 2020.
Abstracts numbered 329-436 and all late-breaking abstracts were presented on Wednesday, February 12, 2020.
Late-breaking abstract presenters should look for their poster number starting with LB- at the end of the regular poster section on Wednesday.

All poster sessions were from 4:30-6:30 PM in the Exhibit Hall.

ePosters in Exhibit Hall and in Mobile App

In addition, all poster presenters were required to submit an electronic version of their poster to be available to attendees throughout WORLDSymposium 2020.

Details on ePoster submission were sent to all first authors. Deadline for uploading ePosters was February 3, 2020.

All registered attendees had access to the ePosters at electronic kiosks in the Exhibit Hall, during Exhibit hours at WORLDSymposium. The ePosters are NOT available after the close of the conference.

WORLDSymposium™ 2020 Full Program on Lysosomal Diseases

Mon. Feb. 10 Tues. Feb. 11 Wed. Feb. 12 Thurs. Feb. 13

Emerging Trends (Monday 8:00-11:30 AM); Basic and Bench Science (Monday 1:00-4:30 PM).
Following Emerging Trends in the morning and the Young Investigator Awards, presentations in the afternoon session discussed innovations in technology and how they can be applied to early diagnosis for lysosomal conditions, progress in gene therapy, and exploitation of differences at the cellular level that may indicate early disease state. Download the WORLDSymposium 2020 program (PDF 150KB).

8:00	Pre-Conference Symposium	Emerging Trends: State-of-the-Art for Experts (Registration required)
11:30	Lunch – On Own

Basic Science I: Disease Mechanisms, Pathology, and Biomarkers of Lysosomal Diseases

Co-Chairs: Jill A. Morris & Danilo A. Tagle

1:00	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome & Announcements Presentation of 2020 Young Investigator Award
1:15	Soumeya Bekri Rouen University Hospital Rouen, France	Predictive biological patterns in Fabry disease revealed by integrative omics machine learning analysis
1:30	Anastasia G. Henry Denali Therapeutics South San Francisco, CA, United States	Brain delivery and efficacy of an intravenously-administered lysosomal enzyme using a blood-brain barrier transport vehicle
1:45	Petra Oliva ARCHIMEDlife Vienna, Austria	Differential diagnosis of Niemann-Pick disease types A and B in cases of suspected Gaucher disease
2:00	Shaun C. Bolton University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom	International Niemann-Pick Disease Registry (INPDR): The characteristics of ASMD and NPC patients
2:15	Ibane Abasolo Vall d’Hebron Institute of Research Barcelona, Spain	Extracellular vesicles increase the enzymatic activity of lysosomal proteins and improve the efficacy of enzyme replacement therapy in Fabry disease
2:30	Behzad Najafian University of Washington Seattle, WA, United States	Podocyte globotriaosylceramide (GL-3) content in female adult patients with Fabry disease and amenable mutations reduces following 6 months of treatment with migalastat
2:45	Break
3:15	Weihua Tian University of Copenhagen Copenhagen, Denmark	Long-acting glyco-design (LAGD) for improved kinetics and distribution of α-galactosidase A
3:30	Poulomee Bose Centre Hospitalier Universitaire Sainte-Justine (CHU St. Justine) Montreal, QC, Canada	Early synaptic dysfunction in MPS IIIC
3:45	Takumi Era IMEG, Kumamto University Kumamoto, Japan	Presynaptic dysfunction in neurons derived from Tay-Sachs-iPSCs
4:00	Sarah Kim University of Minnesota Minneapolis, MN, United States	Quantification of cerebrospinal fluid chitotriosidase in a clinical laboratory is validated for use in diagnosis and clinical trials
4:15	Mohammad A. Hossain Advanced Clinical Research Centre Kawasaki, Kanagawa, Japan	DNA methylation study of GLA gene and its association with autophagy and clinical severity of heterozygous Fabry disease females
4:30	Poster Reception in the Exhibit Hall

Basic and Bench Science (Tuesday 7:30-11:30 AM). Basic and bench science presentations continued on Tuesday morning after the presentation of the Roscoe O. Brady Award for Innovation and Accomplishment, and featured award recipient presentation. Translational Research (Tuesday 1:00-4:30 PM). Presentations in these sessions turn to the challenge of moving laboratory discoveries to therapy, the important hurdles of translational research. Some broad topics of discussion included modulation of CNS affects of disease, how to increase the efficacy of therapeutic modalities, and genotype/phenotype correlations. Download the WORLDSymposium 2020 program (PDF 150KB).

Basic Science II: Developing Therapeutic Approaches in the Laboratory

Co-Chairs: Brian Bigger & Sarah Kim

6:15	Satellite Symposia
7:30	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome & Presentation of 2020 Roscoe O. Brady Award for Innovation and Accomplishment
7:45	John F. Crowley Amicus Therapeutics, Inc. Cranbury, NJ, United States	2020 Roscoe O. Brady Award for Innovation and Accomplishment Address: The Moral Obligation to Ensure Access to Medicines for All Patients in Need
8:15	Jeffrey Y. Huang Children’s Hospital of Orange County Orange, CA, United States	Longitudinal assessment and immune response to recombinant GAA in CRISPR-Cas9 generated Pompe disease knock-in mice
8:30	Maria Dolores Ledesma Centro Biologia Molecular Severo Ochoa Madrid, Spain	Inhibition of fatty acid amide hydrolase prevents pathology in a mouse model of acid sphingomyelinase deficiency by rescuing downregulated endocannabinoid signalling
8:45	Rebecca C. Ahrens-Nicklas The Children’s Hospital of Philadelphia Philadelphia, PA, United States	Efficacy of cell-type specific rescue in a new mouse model of CLN3 disease
9:00	Vera Niederkofler QPS Austria GmbH Grambach, Austria	Neuroinflammation in mouse models of two different lysosomal diseases
9:15	Kimmo Lehtimäki Charles River Discovery Kuopio, Finland	Longitudinal characterization of the Cln8^mnd-/- mouse model of CLN8 Batten disease fine motor performance, retinal degeneration, brain pathology, and metabolic changes
9:30	Lalitha Belur University of Minnesota Minneapolis, MN, United States	Systemic high-level IDUA enzyme activity with correction of neurologic deficit in mucopolysaccharidosis type I mice by ex vivo lentiviral transduction of hematopoietic stem cells
9:45	Break & Exhibits
10:15	Dao Pan Cincinnati Children’s Hospital Medical Center Cincinnati, OH, United States	miR-143 regulates lysosomal enzyme transport across blood-brain barrier and improves CNS treatment for Hurler syndrome
10:30	Natalia Gomez-Ospina Stanford University Stanford, CA, United States	Monocyte lineage-specific glucocerebrosidase expression in human hematopoietic stem cells: A universal genome editing strategy for Gaucher disease
10:45	Malte Lenders University Hospital Muenster Muenster, Germany	Neutralizing anti-drug antibodies inhibit endothelial enzyme uptake and activity in Fabry disease
11:00	Zully Pulido Pontificia Universidad Javeriana Bogotá D.C., Colombia	Recombinant hexosaminidases conjugated to magnetite nanoparticles: Alternative therapeutic treatment routes in GM2 fibroblasts
11:15	Elena V. Batrakova University of North Carolina Durham, NC, United States	Extracellular vesicles as drug delivery vehicles for lysosomal enzyme TPP1 to treat Batten disease
11:30	Lunch – On Own or Satellite Symposia	Exhibit hall is open
11:45	Satellite Symposia

Translational Research I

Co-Chairs: Joseph J. Orsini & Amy Gaviglio

1:00	Brian Kevany Abeona Therapeutics Cleveland, OH, United States	A novel AAV capsid with improved tropism to heart, kidney and PNS for treatment of Fabry disease
1:15	Li Ou University of Minnesota Minneapolis, MN, United States	Liver-targeting gene editing achieves significant neurological benefits in MPS I mice
1:30	Scott Kerns Abeona Therapeutics Cleveland, OH, United States	Combination AAV delivery to target vision loss and CNS manifestations in CLN3 disease
1:45	Halil Dundar Gazi University Faculty of Medicine Ankara, Turkey	Triamterene-induced suppression of R227X premature termination codon in Fabry disease
2:00	Marisa Eve Pulcrano University of California, San Francisco San Francisco, CA, United States	Translating a novel fetal therapy for lysosomal diseases into clinical care: The race for approval to treat one patient with mucopolysaccharidosis type VII
2:15	Paul J. Orchard University of Minnesota Minneapolis, MN, United States	High dose hematopoietic stem cell transplantation leads to rapid hematopoietic and microglial recovery and disease correction in a mouse model of Hurler syndrome
2:30	Ari Zimran Shaare Zedek Medical Center Jerusalem, Israel	Real life data on the safety and efficacy of ambroxol for patients with Gaucher disease or GBA-related Parkinson disease
2:45	Break & Exhibits
3:15	Michael H. Gelb University of Washington Seattle, WA, United States	A universal newborn and diagnostic screening platform for lysosomal diseases and beyond
3:30	Melissa Wasserstein Children’s Hospital at Montefiore Bronx, NY, United States	“ScreenPlus”: A comprehensive, dynamic, multi-disorder newborn screening pilot program
3:45	Ankit K. Desai Duke University Durham, NC, United States	Benefits of prophylactic short-course immunomodulation in patients with infantile Pompe disease: Demonstration of long-term safety and efficacy in a large cohort
4:00	Dominique P. Germain University of Versailles– St. Quentin en Yvelines (UVSQ) Montigny, France	The benefits, challenges and regional differences of family screening in rare genetic diseases: Lessons from Fabry disease
4:15	Dau-Ming Niu Taipei Veterans General Hospital Taipei, Taiwan	Early detection of the irreversible cardiac damages in the adults with late onset Fabry disease in a large cohort study via newborn screening
4:30	Poster Reception in the Exhibit Hall
6:30	Satellite Symposia

Translational Research (Wednesday 7:30-11:30 AM). Presentations in these sessions turned to the challenge of moving laboratory discoveries to therapy, the important hurdles of translational research. Some broad topics of discussion included modulation of CNS affects of disease, how to increase the efficacy of therapeutic modalities, and genotype/phenotype correlations. Clinical Trials for Registration and Clinical Outcomes (Wednesday 1:00-4:30 PM). These sessions were committed to presentations of results from clinical trials, in most cases, the actual application of new agents in humans affected by these conditions. These sessions included presentations related to re-thinking the definition of biomarkers for lysosomal disease. Download the WORLDSymposium 2020 program (PDF 150KB).

Translational Research II

Co-Chairs: Philip J. Brooks & Ellen Sidransky

6:15	Satellite Symposia
7:30	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome & 2020 Patient Advocate Leader Announcement and Presentation to Cara O’Neill
7:45	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Keynote Address: Navigating Clinical Trials
8:15	Nicholas A. Bascou University of Pittsburgh Medical Center (UPMC) Children’s Hospital of Pittsburgh Pittsburgh, PA, United States	A prospective natural history study of metachromatic leukodystrophy: A 20 year study
8:30	Derralynn A. Hughes University College London London, United Kingdom	First-in-human study of a liver-directed AAV gene therapy (FLT190) in Fabry disease
8:45	Margaret McGovern Stony Brook School of Medicine Stony Brook, NY, United States	Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: Eleven years of observation
9:00	Donna L. Bernstein Mount Sinai School of Medicine New York, NY, United States	Lysosomal acid lipase deficiency and hematologic cancer predisposition
9:15	Jane Louise Kinsella Royal Manchester Children’s Hospital Manchester, United Kingdom	Case report of the first patient treated with ex-vivo autologous haematopoietic stem cell gene therapy transplant in mucopolysaccharidosis type IIIA
9:30	Fulvio Mavilio Audentes Therapeutics San Francisco, CA, United States	Pre-clinical safety and efficacy findings of AT845, a novel gene replacement therapy for Pompe disease targeting skeletal muscle and heart
9:45	Break & Exhibits
10:15	George Karkashadze Scientific Research Institute of Pediatrics and Child Health CCH RAoS Moscow, Russian Federation	Abnormalities in the cerebral cortex in Gaucher disease type 1: Findings from the ENIGMA storage disease working group
10:30	Erik A. Lykken University of Texas (UT) Southwestern Medical Center Dallas, TX, United States	Combination intrathecal and intravenous gene therapy reveals a dominant role for treatment age in determining survival and behavioral outcomes in the mouse model of infantile neuronal ceroid lipofuscinosis
10:45	Jacinthe Gingras Homology Medicines Bedford, MA, United States	HMI-202: Investigational gene therapy for treatment of metachromatic leukodystrophy (MLD)
11:00	Umut Cagin Genethon Évry, France	Liver expression of secretable GAA rescues advanced Pompe disease at the biochemical, functional, and transcriptional level in Gaa-/- mice
11:15	Carlos J. Miranda Freeline Therapeutics Stevenage, United Kingdom	One-off liver directed AAV gene therapy achieves long term uptake of acid beta-glucocerebrosidase by macrophages of affected tissues in Gaucher disease
11:30	Lunch – On Own or Satellite Symposia	Exhibit hall is open
11:45	Satellite Symposia

Clinical Trials I: Clinical Trials for Registration

Co-Chairs: Stephen C. Groft & Tiina K. Urv

1:00	John Mitchell Montreal Children’s Hospital Montreal, QC, Canada	Farber disease (acid ceramidase deficiency) natural history study: Prospective and retrospective clinical data
1:15	Manisha Balwani Icahn School of Medicine at Mount Sinai Hospital New York, NY, United States	Clinical manifestations of lysosomal acid lipase deficiency (LAL-D): The international LAL-D Registry
1:30	Christoph Schwering University Medical Center Hamburg- Eppendorf Hamburg, Germany	Development of the “Hamburg best practice guidelines for ICV-enzyme replacement therapy (ERT) in CLN2 disease” based on 5 years treatment experience in 48 patients
1:45	George Diaz Icahn School of Medicine at Mount Sinai New York, NY, United States	Preliminary data from first clinical trial of enzyme replacement therapy with olipudase alfa in pediatric patients with chronic visceral and neurovisceral acid sphingomyelinase deficiency
2:00	Nuthana Prathivadi Bhayankaram Royal Manchester Children’s Hospital Manchester, United Kingdom	Umbilical cord blood transplant is the preferred stem cell source in children with MPS IH (Hurler syndrome) undergoing hematopoietic stem cell transplantation
2:15	Kevin M. Flanigan Nationwide Children’s Hospital Columbus, OH, United States	Interim results of Transpher A, a multicenter, single-dose, phase 1/2 clinical trial of ABO-102 gene therapy for Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA)
2:30	Frits Wijburg Amsterdam UMC Amsterdam, Netherlands	Phase 2-3 gene therapy trial using adeno-associated virus vector for patients with mucopolysaccharidosis type IIIA
2:45	Break & Exhibits
3:15	Kim L. McBride Nationwide Children’s Hospital Columbus, OH, United States	Safety, tolerability and preliminary evidence of biopotency in Transpher B, a multicenter, single-dose, phase 1/2 clinical trial of ABO-101 gene therapy for Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB)
3:30	Raymond Y. Wang Children’s Hospital of Orange County (CHOC) Children’s Specialists Orange, CA, United States	Long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis type VII
3:45	Julia B. Hennermann University Medical Center Mainz Mainz, Germany	Puberty, fertility and pregnancy in patients with mucopolysaccharidosis and mucolipidosis: A multicentre cross-sectional study
4:00	Torayuki Okuyama National Center for Child Health and Development Tokyo, Japan	Therapy for MPS II with an intravenous blood-brain barrier-crossing enzyme (JR-141): 26-week results from a phase 3 study in Japan suggesting significant efficacy against central nervous system and systemic symptoms
4:15	Marc Patterson Mayo Clinic Rochester, MN, United States	Efficacy and safety of arimoclomol in patients with Niemann-Pick disease type C: Results from a double-blind, randomized placebo-controlled trial with a novel treatment
4:30	Poster Reception in the Exhibit Hall
6:30	Satellite Symposia

Clinical Trials for Registration and Clinical Outcomes (Thursday 7:30-11:30 AM). These sessions were committed to presentations of results from clinical trials, in most cases, the actual application of new agents in humans affected by these conditions. These sessions included presentations related to re-thinking the definition of biomarkers for lysosomal disease. NEW: Industry Contemporary Forum (Non-CME) (Thursday, 1:00-4:30 PM). These non-CME platform presentations were specifically for corporate first authors and provided attendees with cutting-edge industry research, data and developments. Industry authors who submitted an abstract prior to the October 1, 2019 deadline and selected the abstract category “Contemporary Forum” were included in the abstract review and selection process for this session. (Abstracts from all other categories may be included here if the first author is from industry.) Download the WORLDSymposium 2020 program (PDF 150KB).

Clinical Trials II: Clinical Outcomes

Co-Chairs: Yoshikatsu Eto & Priya S. Kishnani

6:15	Satellite Symposia
7:25	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome
7:30	Peter Marks Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD, United States	Keynote Address: The Shift from Personalized to Individualized Therapies
8:00	Samuel Gröschel University Children’s Hospital Tübingen, Germany	Effect of intrathecal recombinant human arylsulfatase A enzyme replacement therapy on structural brain MRI in children with metachromatic leukodystrophy
8:15	Francesca Fumagalli San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute Milano, Italy	Lentiviral hematopoietic stem and progenitor cell gene therapy (HSPC-GT) for metachromatic leukodystrophy (MLD): Clinical outcomes from 33 patients
8:30	Emily de los Reyes Nationwide Children’s Hospital Columbus, OH	Single-dose AAV9-CLN6 gene transfer stabilizes motor and language function in CLN6-type Batten disease: Interim results from the first clinical gene therapy trial
8:45	David G. Warnock University of Alabama Birmingham, CA, United States	Pegunigalsidase alfa, a novel PEGylated ERT, evaluated in Fabry disease patients with progressing kidney disease, RCT study design
9:00	Christoph Wanner University of Würzburg Würzburg, Germany	Rationale and design of the MODIFY study: A phase 3 multicenter, double-blind, randomized, placebo-controlled, parallel-group study to determine the efficacy and safety of lucerastat oral monotherapy in adult subjects
9:15	Raphael Schiffmann Baylor Research Institute Dallas, TX, United States	Venglustat combined with imiglucerase positively affects neurological features and brain connectivity in adults with Gaucher disease type 3
9:30	Pramod K. Mistry Yale University School of Medicine New Haven, CT, United States	Individual patient responses to eliglustat in treatment-naïve adults with Gaucher disease type 1: Final data from the phase 3 ENGAGE trial
9:45	Break
10:15	David Kronn New York Medical College Valhalla, NY, United States	Mini-COMET study: Safety, immunogenicity, and preliminary efficacy for repeat avalglucosidase alfa dosing in patients with infantile-onset Pompe disease (IOPD) who were previously treated with alglucosidase alfa and demonstrated clinical decline
10:30	Mazen M. Dimachkie University of Kansas Medical Center Kansas City, KS, United States	NEO1 and NEO-EXT studies: Long-term safety and exploratory efficacy of repeat avalglucosidase alfa dosing for 5.5 years in late-onset Pompe disease patients
10:45	Stephanie Austin Duke University Durham, NC, United States	Extended treatment with VAL-1221, a novel protein targeting cytoplasmic glycogen, in patients with late-onset Pompe disease
11:00	Paul Harmatz University of California – San Francisco (UCSF) Benioff Children’s Hospital Oakland, CA, United States	A new randomized placebo controlled study to establish the safety and efficacy of velmanase alfa (human recombinant alpha-mannosidase) enzyme replacement therapy for the treatment of alpha-mannosidosis
11:15	Angela Schulz University Medical Center Hamburg-Eppendorf Hamburg, Germany	Cerliponase alfa for the treatment of CLN2 disease in an expanded patient cohort including children younger than three years: Interim results from an ongoing clinical study
11:30	Lunch – On Own or Satellite Symposia
11:45	Satellite Symposia

Contemporary Forum

Co-Chairs: R. Scott McIvor & Anne R. Pariser

The following session is not available for CME/CE accreditation; CEU credits for GCs may apply.

1:00	Dwight Koeberl Duke University School of Medicine Durham, NC, United States	A phase 1 study of gene therapy with ACTUS-101 in late-onset Pompe disease
1:15	Sean M. Armour Spark Therapeutics, Inc. Philadelphia, PA, United States	Preclinical development of SPK-3006, an investigational liver-directed AAV gene therapy for the treatment of Pompe disease
1:30	Alissa Brandes Prevail Therapeutics New York, NY, United States	Gene therapy PR006 increased progranulin levels and improved lysosomal related phenotypes in model systems
1:45	Birgitte Volck AVROBIO, Inc. Cambridge, MA, United States	Gb3 substrate in endothelial cells of renal peritubular capillaries was reduced in a previously untreated classic Fabry male patient treated with AVR-RD-01 investigational lentiviral gene therapy
2:00	Lin Liu M6P Therapeutics St. Louis, MO, United States	A new platform technology for next generation lysosomal enzyme replacement and potential gene therapy in the treatment of lysosomal diseases
2:15	Manolo Bellotto Gain Therapeutics Lugano, Switzerland	Brain penetrant structurally targeted allosteric regulators for treating GLB1-related disorders
2:30	Julie C. Ullman Denali Therapeutics South San Francisco, CA, United States	Novel FACS based method demonstrates CNS cell-type distribution and efficacy of a BBB penetrant ERT in a mouse model of MPS II
2:45	Break
3:15	William Casey Hallows Codexis Redwood City, CA, United States	Engineering α-galactosidase A (GLA) to improve protein stability, efficacy and reduced immune response for the treatment of Fabry disease
3:30	Nicholas France E-Scape Bio, Inc. San Francisco, CA, United States	Sphingosine-1-phosphate receptor type 5 (S1P5) agonism: A potential new mechanism for the treatment of neuronopathic features of Niemann-Pick disease type C and neurodegenerative sphingolipidoses
3:45	Linda Ingemann Orphazyme A/S Copenhagen N, Denmark	Rescue of NPC1 protein and effect on biomarkers by arimoclomol treatment in Niemann-Pick disease type C
4:00	Emanuela Izzo BioMarin Pharmaceutical Inc. Novato, CA, United States	Utility of gene panel testing in children with seizure onset after 2 years of age: Results from a European and Middle Eastern epilepsy genetic testing program
4:15	R. Scott McIvor Immusoft Corporation Seattle, WA, United States	Iduronidase-transposed human B lymphocytes correct enzyme deficiency and glycosaminoglycan storage disease in immunodeficient MPS I mice
4:30-5:30	Networking Reception
5:00-7:00	Lysosomal Disease Network (LDN) Annual Meeting

John F. Crowley, MD received the 2020 Roscoe O. Brady Award for Innovation and Accomplishment

John F. Crowley is the Chairman and CEO of Amicus Therapeutics, a global biotechnology company focusing on developing treatments for rare genetic diseases. John has been Amicus CEO since 2005 and has overseen the company’s growth from a four person start-up to one with operations in more than 30 countries, with 550+ employees and a market value of nearly $3 billion. John’s involvement with biotechnology stems from the 1998 diagnosis of two of his children with Pompe disease—a severe and often fatal neuromuscular disorder. In his drive to find a cure for them, he left his position at Bristol-Myers Squibb and became an entrepreneur as the Co-founder, President and CEO of Novazyme Pharmaceuticals, a biotech start-up conducting research on a new experimental treatment for Pompe disease (which he credits as ultimately saving his children’s lives). In 2001, Novazyme was acquired by Genzyme Corporation and John continued to play a lead role in the development of a drug for Pompe disease as Senior Vice President, Genzyme Therapeutics.

John and his family have been profiled on the front page of The Wall Street Journal and are the subjects of a book by Pulitzer prize-winning journalist Geeta Anand, “The Cure: How a Father Raised $100 Million-And Bucked the Medical Establishment-In a Quest to Save His Children.” The major motion picture, Extraordinary Measures, starring Brendan Fraser and Harrison Ford, is inspired by the Crowley family journey. John is the author of a personal memoir: Chasing Miracles: The Crowley Family Journey of Strength, Hope, and Joy.

John served as a commissioned intelligence officer in the U.S. Navy Reserve from 2005-2016, assigned to the United States Special Operations Command and is a veteran of the global war on terrorism, with service in Afghanistan. He graduated with a B.S. in Foreign Service from Georgetown University, and earned a J.D. from the University of Notre Dame Law School and an M.B.A. from Harvard. The Crowley family was the recipient of the 2011 Family Exemplar Award from the University of Notre Dame. He is also a member of the University Council on Science & Technology at Notre Dame. John served as the National Chairman of the Make-A-Wish Foundation of America (2014-2016) and is a founding Board member of the Global Genes Project. John is a Henry Crown Fellow at the Aspen Institute.

Mr. Crowley received the 2020 WORLDSymposium Roscoe O. Brady Award for Innovation and Accomplishment on Tuesday, February 11, 2020 at 7:30 AM following which he gave his address The Moral Obligation to Ensure Access to Medicines for All Patients in Need.

Cara O’Neill, MD received the WORLDSymposium™ 2020 Patient Advocate Leader (PAL) Award

Cara O’Neill, MD, is the Chief Science Officer at Cure Sanfilippo Foundation, a pediatrician, and mother to a daughter with the rare disease Sanfilippo syndrome (MPS III). Dr. O’Neill completed her medical education at West Virginia University School of Medicine and subsequently her Pediatric Residency training at the University of South Carolina. She has worked both in private practice and academic settings. During her tenure as an Assistant Professor of Clinical Pediatrics at the University of South Carolina, she helped train medical students and residents, and practiced in a clinic specific to children with special healthcare needs. Dr. O’Neill’s uniquely-paired career and life experiences allow her to bridge gaps between scientists, clinicians, industry, and families, helping foster patient-centered research and future translational paths for rare disease treatments.

Dr. ONeill and her husband founded Cure Sanfilippo Foundation after receiving her daughter’s diagnosis in 2013, guided by the mission to support the creation of treatments and an eventual cure for the disease. Since then, they have spread awareness around the globe about Sanfilippo syndrome via talk shows, news media, online platforms, and international newspapers. Dr. O’Neill leads patient-focused research efforts within the foundation and has presented at international conferences and authored peer-reviewed journal articles. In addition, she collaborates with other non-profit groups on mutual advocacy and research interests, as well as oversees the foundation’s funding of external scientific programs.

Dr. O’Neill lives in Columbia, SC, with her husband Glenn, son Beckham, and daughter Eliza.

On Wednesday, February 12, 2020 at 7:30 AM, Cara was presented with the WORLDSymposium 2020 Patient Advocate Leader Award.

Chester B. Whitley, PhD, MD Delivered Keynote Address on Wednesday, February 12, 2020

Dr. Whitley is the Principal Investigator for the Lysosomal Disease Network (LDN), a growing consortium of medical centers collaborating since 2003—and funded by the National Institutes of Health beginning in 2008—to address critical gaps in taking lysosomal disease research from the lab to clinical practice. Chester (Chet) B. Whitley, Ph.D., M.D. is a tenured Professor in the Department of Pediatrics, the Department of Experimental and Clinical Pharmacology, and Director of the Advanced Therapies Program at the University of Minnesota.

In 1983, he conducted the first US trials of bone marrow transplantation for Hurler syndrome, other mucopolysaccharidoses, and selected lysosomal diseases including Krabbe disease and Tay-Sachs disease. With the first transplant for Hurler syndrome in the USA. (September 13, 1983, University of Minnesota)¹ and the continuing clinical trials during the next decade², he characterized the level of response and clinical outcomes. In the case of Hurler syndrome, cognitive testing and imaging showed protection of the brain despite the seemingly impenetrable blood-brain barrier. As the very first efficacious treatment for a lysosomal disease, hematopoietic stem transplant provided the proof-of-principle for development of future enzyme replacement therapies, gene therapy, and other systemic treatments. During these early transplant studies, Dr. Whitley expanded upon the 1960’s “cross-correction” observations at NIH in cultured fibroblasts, and coined the term “metabolic cross-correction” and characterized multiple different mechanisms accounting for the clinical responses in patients. In conversation with the US FDA in the early 1990’s, he coined the term “ultra-orphan disease” to differentiate those conditions that are orders of magnitude more rare than the legislated definition of “orphan disease” with prevalence of <200,000.

In the late 1990s, Dr. Whitley conducted the first clinical trial of gene therapy for a mucopolysaccharidosis condition, Hunter syndrome^3,4. At that time, he invented⁵ the DMB dye-binding test for measuring urine glycosaminoglycans (GAG), the most common method for quantifying GAG in diagnostic laboratories globally.

He is also responsible for a number of other ‘firsts’: (a) discovering a ‘pseudo-deficiency’ allele for MPS^6,7; (b) finding that combining therapies, e.g., enzyme replacement therapy (ERT) after bone marrow transplantation⁸ may enhance metabolic correction; (c) demonstrating that small amounts of intravenous laronidase enzyme cross the blood-brain barrier and reduces the pathology in the brain, and improves the learning of mice with Hurler syndrome⁹; and, recently, (d) that intravenous zinc-finger nuclease gene-editing prevents brain disease in mice with Hurler syndrome¹⁰ and Hunter syndrome¹¹.

Dr. Whitley conceived and organized the 1st International Symposium on Mucopolysaccharidosis and Related Diseases (May 20-23, 1988, Minneapolis, Minnesota)¹². He is also Director of the Gene Therapy Center at the University of Minnesota, supported by an NIH program project grant “Gene Therapy for Metabolic Disease” for two decades (5P01HD032652).

He is the founding Principal Investigator of the NIH-funded Lysosomal Disease Network, coordinating 21 clinical studies at 18 institutions. Dr. Whitley is the founding organizer (May 12-15, 2004, Minneapolis, MN USA) and current course director of the annual We’re Organizing Research on Lysosomal Diseases scientific meeting – WORLDSymposium – an international forum that fuses basic, translational and clinical research on lysosomal diseases.

The subject of Dr. Whitley’s Keynote Address was “Navigating Clinical Trials” describing how the community — treatment sponsors (pharmaceutical companies, biotech, and academic clinical trial investigators, the regulatory authorities, and patients — are facing new challenges in bringing a growing number of treatments through the regulatory review process to commercialization and broad distribution. The nature of one-time gene therapy treatments, and a diminishing group of naïve subjects, are creating new issues never seen before.

Peter Marks Delivered Keynote Address on Thursday, February 13, 2020

The WORLDSymposium Planning Committee is excited to announce Peter Marks, MD, PhD, will provide the Keynote Address on Thursday, February 13, 2020 at the 16th Annual WORLDSymposium Scientific Meeting in Orlando, Florida, USA.

Dr. Marks is the director of the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration (FDA). The center is responsible for assuring the safety and effectiveness of biological products, including vaccines, allergenic products, blood and blood products, and cellular, tissue, and gene therapies.

Dr. Marks received his graduate degree in cell and molecular biology and his medical degree at New York University. Following this, he completed an Internal Medicine residency and Hematology/Medical Oncology fellowship at Brigham and Women’s Hospital in Boston, where he subsequently joined the attending staff as a clinician-scientist and eventually served as Clinical Director of Hematology.

He then moved on to work for several years in the pharmaceutical industry on the clinical development of hematology and oncology products prior to returning to academic medicine at Yale University where he led the Adult Leukemia Service and served as Chief Clinical Officer of Smilow Cancer Hospital. He joined the FDA in 2012 as Deputy Center Director for CBER and became Center Director in 2016. Dr. Marks is board certified in internal medicine, hematology and medical oncology, and is a Fellow of the American College of Physicians.

Dr. Marks is a renowned speaker and expert in numerous areas, including the current issues facing gene therapy research not only in the Unites States, but also from a global perspective. Dr. Marks presented “The Shift from Personalized to Individualized Therapies” as the Keynote Address on Thursday, February 13, 2020 at 7:30 AM.

Whitley CB, Ramsay NKC, Kersey JH, Krivit W: Bone marrow transplantation for Hurler syndrome. Assessment of metabolic correction. Birth Defects 22:7-24, 1986.
Whitley CB, Belani K, Chang PN, Summers CG, Blazar BR, Tsai MY, Latchaw RE, Ramsay NKC, Kersey JH: Long-term outcome of Hurler syndrome following bone marrow transplantation, Am J Med Genet 46:209-218, 1993.
U.S. Food and Drug Administration BB-IND: #5370; Autologous Peripheral Blood Stem Cells Cultured Ex-Vivo with Anti-CD3 (OKT3, Ortho) and Interleukin-2 (Chiron); Transduced (L2SN, University of Minnesota) Expressing IDS Gene; approved to initiate clinical trial (June, 1995). Active clinical trial period: – January 10, 1998.
NIH Recombinant DNA Advisory Committee application; Retroviral-Mediated Transfer of the Iduronate-2-Sulfatase Gene Into Lymphocytes for Treatment of Mild Hunter Syndrome (Mucopolysaccharidosis Type II), Human Gene Therapy Protocol, University of Minnesota Medical School, Minneapolis, MN, Chester B. Whitley, Ph.D., M.D., R. Scott McIvor, Ph.D., Susan A. Berry, M.D., Bruce R. Blazar, M.D., John H. Kersey, M.D., Richard A. King, M.D., Ph.D., Anthony J. Faras, Ph.D., Richard E. Latchaw, M.D., Jeffrey J. McCullough, M.D.,
Norma K.C. Ramsay, M.D.
Method for the Detection of Mucopolysaccharide Disease (Serial No. 194,553) submitted May 13, 1988; continuation-in-part (Serial No. 07/297,051) submitted January 16, 1989; amendment, Method for the detection of mucopolysaccharide storage disease, continuation-in-part (Serial No. 07/297,051) submitted May 29, 1991; patent allowed, November, 1993; patent application (Serial No. 07/806,833) Method for the Detection of Mucopolysaccharide Storage Diseases issued on May 10, 1994 as U.S. Patent No. 5,310,646.
Whitley CB, Gorlin RJ, Krivit W. A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome. Am J Med Genet 28(1). 1987. 233-243. PMID: 3118714.
Aronovich EL, Pan D, Whitley CB, Molecular genetic defect underlying alpha-L-iduronidase pseud
odeficiency. Am J Hum Genet. 1996 Jan;58(1):75-85. PMCID: PMC1914939.
Whitley CB, Utz JR. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): a single dose of galsulfase further reduces urine glycosaminoglycans after hematopoietic stem cell transplantation. Mol Genet Metab 101(4). 2010. 346-348. PMID: 20800524.
Ou, L., DeKelver R.C., Rohde M., Tom S., Radeke R., St. Martin S., Santiago,Y, Sproul S., Przybilla M.J., Koniar B.L., Podetz-Pedersen K.M., Laoharawee K., Cooksley R.D., Meyer K.E., Holmes M.C., McIvor R.S., Wechsler T., Whitley C.B. ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome, Molecular Therapy (2018), doi: https://doi.org/10.1016/j.ymthe.2018.10.018.
Ou, L., DeKelver R.C., Rohde M., Tom S., Radeke R., St. Martin S., Santiago,Y, Sproul S., Przybilla M.J., Koniar B.L., Podetz-Pedersen K.M., Laoharawee K., Cooksley R.D., Meyer K.E., Holmes M.C., McIvor R.S., Wechsler T., Whitley C.B. ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome, Molecular Therapy (2018), doi: https://doi.org/10.1016/j.ymthe.2018.10.018.
K. Laoharawee, R. DeKelver, K. Podetz-Pedersen, M. Rohde, S. Sproul, H. Nguyen, T. Nguyen, S.S. Martin, L. Ou, S. Tom, C.B. Whitley, R.S. McIvor. Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-mediated In Vivo Genome Editing. Molecular Therapy 26(4):1127-1136, April 2018. doi.org/10.1016/j.ymthe.2018.03.002
Whitley, CB, J.M. Opitz, J.F. Reynolds. First International Congress on Mucopolysaccharidosis and Related Diseases ‐ 70 Years of Research, University of Minnesota, Minneapolis, May 20–23, 1988. Am J Med Genet 32(2) 1989. doi.org/10.1002/ajmg.1320320233

2021 Emerging Trends in Lysosomal Biology & Lysosomal Diseases: State-of-the-art for Experts

Sunday, February 7, 2021 – March 15, 2021: On-Demand Only

For the ninth consecutive year, WORLDSymposium™ began with “Emerging Trends”. This half day CME/CE course provided a state-of-the-art update for experts working in lysosomal biology and lysosomal diseases. This course was a summary of the latest research trends and other advances in the field.

Emerging Trends was a pre-recorded virtual-only session that was available to view online starting Sunday, February 7, 2021 at 10:00 AM Eastern Standard Time (EST). After the session concluded at 2:00 PM Eastern Standard Time (EST), it was available to watch on-demand until March 15, 2021.

Seasoned researchers provided a global review of the past years’ advances, a state-of-the-art overview of lysosome biology, diseases and therapies. This review evolves every year, providing a summary of the latest research trends, new knowledge, and other discoveries. The course is intended for researchers and health care practitioners who are interested in being current on recent advances in the basic science, diagnosis, and treatment of lysosomal diseases. This course is taught at the postgraduate level, e.g., those with a PhD, MD, PharmD, DDS, MS, MPH, etc.

The content provides comprehensive information on lysosomal diseases, but does not overlap or replace the scientific data being presented during WORLDSymposium 2021. Registration was Required.

Learning Objectives

Upon completion of this educational activity, the participant should be better able to:

Describe the basic structure, function and molecular biology of lysosomes.
Identify specific lysosomal diseases, their clinical manifestations, and means of diagnosis.
Review current treatments for lysosomal diseases, the potential side effects, and their expected clinical outcomes.
Correlate the molecular biology of lysosomes with clinical features, diagnostic testing, and treatment approaches.

Preliminary Agenda

10:00 AM
Introduction
Chester B. Whitley, PhD, MD

10:05 AM
Lysosomal Function and Pathogenesis
Andrew P. Lieberman, PhD MD

10:25 AM
Clinical Features
Marc C. Patterson, MD

10:45 AM
Newborn Screening
Amy Gaviglio, MS, LCGC

11:05 AM
Break

11:30 AM
Therapies
Jeanine R. Jarnes, PharmD

11:50 AM
FDA Regulatory Review
Patroula Smpokou, MD

12:10 PM
Patient’s Perspective on Experimental Therapies
Cara O’Neill, MD

12:30 PM
Break

1:00 PM
Case Studies
Marc C. Patterson, MD

1:20 PM
SARS-CoV-2 Virus
Chester B. Whitley, PhD, MD

1:40 PM
COVID-19: Clinical Impact and Management
Heather Lau, MD

2:00 PM
Closing Remarks
Chester B. Whitley, PhD, MD

2:05 PM
Adjourn

Invited Facuty

Andrew P. Lieberman, PhD MD
Abrams Collegiate Professor of Pathology
Director of Neuropathology
University of Michigan Medical School
Ann Arbor, Michigan

Amy Gaviglio, MS, LCGC
G2S Corporation
Newborn Screening and Molecular Biology Branch
Division of Laboratory Sciences, NCEH
Centers for Disease Control and Prevention
Minneapolis, MN

Jeanine R. Jarnes, PharmD, BCOP, BCPS
Adjunct Assistant Professor, Experimental and Clinical Pharmacology
College of Pharmacy
University of Minnesota, Fairview
Minneapolis, MN, USA

Patroula Smpokou, MD
Deputy Director
Division of Rare Diseases & Medical Genetics
Office of New Drugs │ CDER | FDA
Silver Spring MD

Cara O’Neill, MD
Chief Science Officer
Cure Sanfilippo Foundation
Pediatrician
Columbia, SC

Heather Lau, MD
Assistant Professor, Department of Neurology
Associate Director, Division of Neurogenetics
Director of the Lysosomal Storage Disorder Program
New York University School of Medicine
Neurogenetics Division
New York, NY

WORLDSymposium™ 2021 Full Program on Lysosomal Diseases

Sun. Feb. 7 Mon. Feb. 8 Tues. Feb. 9 Wed. Feb. 10 Thurs. Feb. 11 Fri. Feb. 12

On Sunday morning, seasoned researchers provided a global review of the past years’ advances, including a state-of-the-art overview of lysosome biology, diseases and therapies (Table 1). This review evolves every year, providing a summary of the latest research trends, new knowledge, and other discoveries. The course is intended for researchers and health care practitioners who are interested in being current on recent advances in the basic science, diagnosis, and treatment of lysosomal diseases. This year, content has been added to address COVID-19 in the context of lysosomal diseases. This course was taught at the postgraduate level, e.g., those with a PhD, MD, PharmD, DDS, MS, MPH, etc. Download the WORLDSymposium 2021 program (PDF 150KB).

	Emerging Trends: State-of-the-Art for Experts	(Registration required)
10:00	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Introduction and Overview of Course
10:05	Andrew P. Lieberman Michigan Medicine University of Michigan Ann Arbor, MI, United States	Lysosomal Function and Pathogenesis
10:25	Marc C. Patterson Mayo Clinic Rochester, MN, United States	Clinical Features
10:45	Amy Gaviglio US Centers for Disease Control and Prevention (CDC) Atlanta, GA, United States	Newborn Screening
11:05	Break
11:30	Jeanine R. Jarnes University of Minnesota Minneapolis, MN, United States	Therapies
11:50	Patroula Smpokou Division of Rare Diseases & Medical Genetics, Office of New Drugs US Food & Drug Administration (FDA) Silver Spring, MD, United States	FDA Regulatory Review
12:10	Cara O’Neill Cure Sanfilippo Foundation Columbia, SC, United States	Patient Advocate’s Perspective on Experimental Therapies
12:30	Break
1:00	Marc C. Patterson Mayo Clinic Rochester, MN, United States	Case Studies
1:20	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	SARS-CoV-2 Virus
1:40	Heather Lau New York University School of Medicine New York, NY, United States	COVID-19: Clinical Impact and Management
1:59	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Closing Remarks
2:00	Adjourn

After the presentation of the Innovation Award, the formal scientific sessions of WORLDSymposium 2021 officially got underway with presentations on laboratory research for lysosomal disease. Presentations during the Basic Science sessions were designed to improve our understanding or prediction of the phenomena involved in lysosomal pathology at a molecular, cellular, and animal model level in order to forwardly think about diagnosis and treatment of lysosomal conditions. These Basic Science sessions were always innovative and presented the latest findings in the field. Download the WORLDSymposium 2021 program (PDF 150KB).

Basic Science

Moderators: Brian Bigger & Dao Pan

8:45	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome & Announcements Presentation of 2021 Roscoe O. Brady Award for Innovation and Accomplishment to Ellen Sidransky
9:00	Ellen Sidransky National Human Genome Research Institute at National Institutes of Health (NIH) Bethesda, MD, United States	Innovation Award Speaker Presentation
9:30	Wei Zhu University of Minnesota Minneapolis, MN, United States	Functional connectivity alterations in MPS I mouse brain at the laminar level revealed by resting-state fMRI *2021 Young Investigator Award Recipient
9:42	Shih-hsin Kan Children’s Hospital of Orange County Orange, CA, United States	iPSC-derived human neural stem cells engraft in the brains of immunocompromised MPS I mice
9:54	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Immunogenicity, genotoxicity, and efficacy of PS gene editing in treating MPS I mice
10:06	Lalitha Belur University of Minnesota Minneapolis, MN, United States	Comparative systemic and neurologic effectiveness of intravenous and intrathecal AAV9 delivered individually or combined in a murine model of mucopolysaccharidosis type I
10:18	Live Moderated Q&A	Wei Zhu, Shih-hsin Kan, Chester B. Whitley, and Lalitha Belur
10:30	Break & Exhibits
11:00	Tyler Harm Iowa State University Ames, IA, United States	Treatment with pentosan polysulfate improves neuropathological measures in the canine model of MPS IIIB *2021 Young Investigator Award Recipient
11:12	Laura López de Frutos Instituto de Investigación Sanitaria Aragón (IIS Aragón) Zaragoza,Spain	Testing new biomarkers for lysosomal diseases
11:24	Ying Sun Cincinnati Children’s Hospital Medical Center Cincinnati, OH, United States	Novel mechanism of SRT and ERT on recovering the function of mitochondrial and autophagy-lysosomal pathway in Gaucher disease neuronal cell model
11:36	Paula Rozenfeld Universidad Nacional de La Plata-CONICET, IIFP La Plata,Argentina	Gaucher disease mesenchymal stem cells showed reduced osteogenesis and increased osteoclastogenesis and adipogenesis
11:48	Live Moderated Q&A	Tyler Harm, Laura López de Frutos, Yin Sun, and Paula Rozenfeld
12:00	Break, Exhibits and Satellite Symposia
1:00	Allen Seylani National Institutes of Health (NIH) Bethesda, MD, United States	Novel regulatory function of GCN5L1 in lysosomal tubulation and biogenesis *2021 Young Investigator Award Recipient
1:12	Behzad Najafian University of Washington Seattle, WA, United States	Direct intercellular cross-correction of α-galactosidase-A deficiency in Fabry disease podocytes through tunneling nanotubes in a mixed cell culture model
1:24	Dau-Ming Niu Taipei Veterans General Hospital Taipei,Taiwan	Development of a gene therapy for Fabry disease using adeno-associated viral vector mediated gene editing
1:36	Stephanie Newman Western University London, ON Canada	AAV9-hARSA decreases sulfatide accumulation in the aged ARSA-/- mouse model for metachromatic leukodystrophy *2021 Young Investigator Award Recipient
1:48	Live Moderated Q&A	Allen Seylani, Behzad Najafian, Dau-Ming Niu, and Stephanie Newman
2:00	Break & Exhibits
2:30	Poster Session
3:30	Break, Exhibits and Networking
4:00	Satellite Symposia

After the presentation of the 2021 Young Investigator Awards and the Patient Advocate Leader (PAL) award, the entirety of the research presentations on Tuesday were dedicated to the Translational Research category. This year, many of the presentations were dedicated to research topics in gene therapy, including innovations occurring in Genetic Therapeutic Approaches in Translation from Laboratory to the Clinic. Download the WORLDSymposium 2021 program (PDF 150KB).

Translational Research

Moderators: PJ Brooks & Jill Morris

9:00	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	2021 Patient Advocate Leader (PAL) Award Announcement and Presentation to Terri L. Klein
9:15	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	2021 Young Investigator Awards Announcement and Presentation
9:30	Xin Chen University of Texas Southwestern Medical Center Dallas, TX, United States	Preclinical results in rodents strongly support clinical evaluation of scAAV9/MFSD8 as a potential gene therapy for CLN7 patients
9:42	Rachel Bailey University of Texas Southwestern Medical Center Dallas, TX, United States	Preclinical studies to support the intrathecal delivery of scAAV9/SUMF1 as a gene replacement therapy for multiple sulfatase deficiency
9:54	Li Ou University of Minnesota Minneapolis, MN, United States	PS gene editing with a novel HEXO construct to treat both Tay-Sachs and Sandhoff diseases
10:06	Su Jin Choi Duke University Durham, NC, United States	Immunosuppression with bortezomib and anti-CD20 mAb is effective in reducing neutralizing antibodies to allow repeated AAV administration in mice *2021 Young Investigator Award Recipient
10:18	Live Moderated Q&A	Xin Chen, Rachel Bailey, Li Ou, and Su Jin Choi
10:30	Break & Exhibits
11:00	Troy Lund University of Minnesota Minneapolis, MN, United States	Biochemical predictors of neurocognitive outcomes in Hurler syndrome
11:12	Jane Kinsella Royal Manchester Children’s Hospital Manchester,United Kingdom	Ex-vivo autologous stem cell gene therapy clinical trial for mucopolysaccharidosis type IIIA: Update on phase I/II clinical trial *2021 Young Investigator Award Recipient
11:24	Bernhard Gentner San Raffaele Telethon Institute for Gene Therapy Milano, Italy	Ex vivo hematopoietic stem cell gene therapy for mucopolysaccharidosis type I (Hurler syndrome)
11:36	Bryan Pukenas University of Pennsylvania Philadelphia, PA, United States	Intracisternal administration of AAV9 gene therapies to target the central nervous system
11:48	Live Moderated Q&A	Troy Lund, Jane Kinsella, Bernhard Gentner, and Bryan Pukenas
12:00	Break, Exhibits and Satellite Symposia
1:00	John Day Stanford University Stanford, CA, United States	A phase I/II open-label gene replacement clinical study for late onset Pompe Disease
1:12	Torayuki Okuyama National Center for Child Health and Development Tokyo,Japan	Prevention of cognitive decline in patients with neuronopathic mucopolysaccharidosis type II treated by intracerebroventricular enzyme replacement therapy: 100-week results of an open-label phase 1/2 study
1:24	Julian Raiman Birmingham Women and Children’s NHS Foundation Trust Birmingham, United Kingdom	Update on safety and efficacy results for phase I/II trial of hydroxypropyl betacyclodextrin (HPâCD) administered intravenously in patients with Niemann-Pick disease type C1
1:36	Calogera Simonaro Icahn School of Medicine at Mount Sinai New York, NY, United States	Modulation of the endocannabinoid receptor CB2 as a novel treatment for the lysosomal diseases
1:48	Live Moderated Q&A	John Day, Torayuki Okuyama, Julian Raiman, and Calogera Simonaro
2:00	Break & Exhibits
2:30	Poster Session
3:30	Break, Exhibits & Networking
4:00	Satellite Symposia

Wednesday began with an important message from Dr. Michael Osterholm, PhD, MPH. Following Dr. Osterholm’s address, WORLDSymposium dedicated the next hour to a discussion on how COVID-19 has affected—and continues to affect—those with lysosomal diseases. After a Question-and-Answer session with Dr. Osterholm, abstract presentations specific to COVID-19 and lysosomal diseases was given. On Wednesday afternoon, the presentations shift to Clinical Applications, including abstracts on Clinical Trials for Registration. Abstracts presented in this category will have a US FDA Investigational New Drug (IND) application for a phase I-III clinical trial or hold an EMA Investigational Medicinal Product Dossier (IMPD) or equivalent. Clinical Outcomes abstracts will also be presented. Download the WORLDSymposium 2021 program (PDF 150KB).

COVID-19 Special Session and Clinical Trials

Maurizio Scarpa & Patroula Smpokou

8:55	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome and Keynote Speaker Introduction
9:00	Michael T. Osterholm University of Minnesota Minneapolis, MN, United States	Keynote Address:The COVID Pandemic: The Evolving Reality
9:30	Live Moderated Q&A	Michael T. Osterholm
9:45	Heather Lau NYU School of Medicine New York, NY, United States	Impact of SARS-CoV-2 on patients with lysosomal diseases in a major NYC hospital system
9:57	Matheus Wilke Hospital de Clinicas de Porto Alegre Porto Alegre, Brazil	Informing patients with rare diseases about COVID-19: Creation of the “Beto and the Coronavirus” booklet
10:09	Siddhee Sahasrabudhe University of Minnesota Minneapolis, MN, United States	Modeling potential interactions between oral Gaucher disease treatment and investigational COVID-19 therapies
10:21	Live Moderated Q&A	Heather Lau, Matheus Wilke, and Siddhee Sahasrabudhe
10:30	Break & Exhibits
11:00	George Diaz Mount Sinai School of Medicine New York, NY, United States	Children treated with olipudase alfa for chronic acid sphingomyelinase deficiency show meaningful improvement on clinically relevant outcomes and an overall favorable safety profile: 1-year results of the ASCEND-Peds trial
11:12	Nicole Muschol UKE – Universitätsklinikum Hamburg-Eppendorf Hamburg, Germany	Tralesinidase alfa (AX 250) enzyme replacement therapy for Sanfilippo syndrome type B
11:24	Emily de los Reyes Nationwide Children’s Hospital Columbus, OH, United States	Single-dose AAV9-CLN6 gene transfer slows the decline in motor and language function in variant late infantile neuronal ceroid lipofuscinosis 6: Interim results from phase 1/2 trial
11:36	Francesca Fumagalli San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute Milan, Italy	Lentiviral hematopoietic stem and progenitor cell gene therapy provides durable clinical benefit in early-symptomatic early-juvenile metachromatic leukodystrophy
11:48	Live Moderated Q&A	George Diaz, Nicole Muschol, Emily de los Reyes, and Francesca Fumagalli
12:00	Break, Exhibits and Satellite Symposia
1:00	Ankit Desai Duke University Medical Center Durham, NC, United States	Transforming the clinical outcomes in CRIM-negative infantile Pompe disease identified via newborn screening: The benefits of early treatment with enzyme replacement therapy and immune tolerance induction
1:12	Melissa Wasserstein Children’s Hospital at Montefiore, Albert Einstein College of Medicine Bronx, NY, United States	Adults with chronic acid sphingomyelinase deficiency show significant visceral, pulmonary, and hematologic improvements after enzyme replacement therapy with olipudase-alfa: 1-year results of the ASCEND placebo-controlled trial
1:24	Ales Linhart General University Hospital and Charles University Prague,Czech Republic	Switching from agalsidase alfa to pegunigalsidase alfa to treat patients with Fabry disease: 1 year of treatment data from BRIDGE, a phase 3 open-label study
1:36	Raphael Schiffmann Baylor Research Institute Dallas, TX, United States	Venglustat combined with imiglucerase positively affects neurological features and brain connectivity in adults with Gaucher disease type 3
1:48	Live Moderated Q&A	Ankit Desai, Melissa Wasserstein, Ales Linhart, and Raphael Schiffmann
2:00	Break & Exhibits
2:30	Poster Session
3:30	Break, Exhibits & Networking
4:00	Satellite Symposia

The third research day of the meeting begins with an address by Peter Marks, MD, PhD. Then, for the second year, the Contemporary Forum allows for presentation of scientific abstracts — Basic, Translational, and Clinical — submitted by industry first-author researchers. Although the first three days of WORLDSymposium are accredited and approved for CME credit, Commercial Interests are not eligible for ACCME accreditation. The Contemporary Forum allows commercial interests to present their work to the WORLDSymposium audience, in this non-CME session, while being held to all the same standards as the ACCME accredited sessions and scored for merit and interest by the same Program Committee. Download the WORLDSymposium 2021 program (PDF 150KB).

Contemporary Forum

Moderators: Mark Sands & Uma Ramaswami

8:45	Chester B. Whitley University of Minnesota Minneapolis, MN, United States	Welcome and Keynote Address Introduction
8:50	Peter Marks Center for Biologics Evaluation and Research US Food & Drug Administration (FDA) Silver Spring, MD, United States	Keynote Address:Trailblazing a Regulatory Framework for Individualized Therapies
9:20	Live Moderated Q&A	Peter Marks
	The following session is not available for CME/CE accreditation (unless noted otherwise); CEU credits for GCs may apply.
9:30	Jeffrey Alexander Spark Therapeutics, Inc Philadelphia, PA, United States	IdeS: An enabling technology to overcome the limitation of neutralizing antibodies to AAV gene therapy
9:42	Marie-Laure Nevoret REGENXBIO Rockville, MD, United States	RGX-121 gene therapy for severe mucopolysaccharidosis type II (MPS II): Interim results of an ongoing first in human trial
9:54	Drew Tietz Sigilon Therapeutics Cambridge, MA, United States	SIG-018: Novel encapsulated non-viral cell-based therapy for MPS II
10:06	Annie Arguello Denali Therapeutics, Inc. South San Francisco, CA, United States	Iduronate-2-sulfatase transport vehicle rescues neurobehavioral and skeletal phenotypes in a mouse model of mucopolysaccharidosis type II
10:18	Live Moderated Q&A	Jeffery Alexander, Marie-Laure Nevoret, Drew Tietz, and Annie Arguello
10:30	Break & Exhibits
11:00	Niek van Til AVROBIO Cambridge, MA, United States	Long-term hematopoietic stem cell gene therapy corrects neuromuscular manifestations in preclinical study of Pompe mice
11:12	Rachel Botham Codexis Redwood City, CA, United States	Engineering α-glucosidase to improve protein stability and cellular uptake for the potential treatment of Pompe disease
11:24	Dustin Armstrong Valerion Therapeutics Concord, MA, United States	VAL-1221: Treating Pompe disease via enhanced glycogen-targeting
11:36	Romuald Corbau Freeline Stevenage, United Kingdom	FLT201: An AAV-mediated gene therapy for type 1 Gaucher disease designed to target difficult to reach tissues
11:48	Live Moderated Q&A	Niek van Til, Rachel Botham, Dustin Armstrong, and Romuald Carbau
12:00	Break, Exhibits and Satellite Symposia
1:00	John Jefferies University of Tennessee Health Science Center Memphis, TN, United States	Utilization of artificial intelligence to identify undiagnosed Fabry disease patients: Development of a validated machine learning model
1:12	Deborah Marsden Ultragenyx Pharmaceutical Inc. Novato, CA, United States	Significant unmet need in infants with mucopolysaccharidosis type VII and non-immune hydrops fetalis: A summary of cases
1:24	Cristina Baricordi AVROBIO, Inc Cambridge, MA, United States	Analysis of genetically engineered stem cell product and follow up of gene therapy patients through high-throughput single cell technologies
1:36	Miganush Stepanians PROMETRIKA, LLC Cambridge, MA, United States	A survey of statistical study design and analysis methods for rare disease development programs
1:48	Live Moderated Q&A	John Jefferies, Deborah Marsden, Cristina Baricordi, and Miganush Stepanians
2:00	Break & Exhibits
2:30	Poster Session
3:30	Break, Exhibits & Networking
4:00	Satellite Symposia

Toward bringing the most recent research to the platform of WORLDSymposium 2021, late-breaking abstract submissions were identified by the Program Committee as being suitable for platform presentation. In order to provide access to the “hot-off-the-presses” content from these researchers, late-breaking abstracts were reviewed and scored, and the top-scoring abstracts were selected for presentation during the 2021 meeting. These abstracts are submitted after the production deadline for publication in this February edition of Molecular Genetics and Metabolism, and as such the full content of these abstracts is available exclusively to registered WORLDSymposium 2021 attendees. Download the WORLDSymposium 2021 program (PDF 150KB).

Late-Breaking

Moderators:Roberto Giugliani & Elizabeth Braunlin

The following session is not available for CME/CE accreditation; CEU credits for GCs may apply.

9:30	Cathal S. Mahon Denali Therapeutics Inc. South San Francisco, CA, United States	Molecular architecture determines brain delivery of transferrin receptor targeted iduronate 2 sulfatase in a mouse model of mucopolysaccharidosis type II
9:42	Jennifer Clarke Matthews Sanofi Framingham, MA, United States	Murine models of lysosomal diseases exhibit differences in brain protein aggregation and neuroinflammation
9:54	Miles C. Smith University of Minnesota Minneapolis, MN, United States	Ex vivo lentiviral transduction of hematopoietic stem cells in mucopolysaccharidosis type II (MPS II) mice achieves high levels of systemic iduronate-2-sulfatase (IDS) enzyme activity and normalization of glycosaminoglycans (GAGs)
10:06	Juana I. Navarrete Hospital Central Sur PEMEX Mexico City, Mexico	Use of biomarkers to follow up positive lysosomal diseases in newborn screening
10:16	Benedikt Schoser Neurologic Clinic Ludwig Maximilian University of Munich Munich, Germany	Top Line Results From the PROPEL Phase 3 Study Comparing AT-GAA (cipaglucosidase alfa/miglustat) versus alglucosidase alfa/placebo in Late Onset Pompe Disease.
10:24	Live Moderated Q&A	Cathal Mahon, Jennifer Clarke Matthews, Miles Smith, Juana Navarrete and Benedikt Schoser
10:40	Break & Exhibits
11:00	Stephanie Cherqui University of California, San Diego La Jolla, CA, United States	Hematopoietic stem cell gene therapy for cystinosis: Updated results from a phase I/II clinical trial
11:12	Priya Kishnani Division of Medical Genetics, Duke University Medical Center Durham, NC, United States	Efficacy and safety results of the avalglucosidase alfa phase 3 COMET trial in late-onset Pompe disease patients
11:24	Mark Thomas Royal Perth Hospital Perth, Australia	AVR-RD-01, an investigational lentiviral gene therapy for Fabry disease: Overview of clinical data from phase 1 and phase 2 studies
11:36	Kevin M. Flanigan Nationwide Children’s Hospital Columbus, OH, United States	Updated results of Transpher A, a multicenter, single-dose, phase 1/2 clinical trial of ABO-102 gene therapy for Sanfilippo syndrome type A (MPS IIIA)
11:48	Live Moderated Q&A	Stephanie Cherqui, Priya Kishnani, Mark Thomas, and Kevin Flanigan
12:00	Break, Exhibits and Satellite Symposia
1:00	Michaël Hocquemiller LYSOGENE Neuilly sur seine, France	CNS-specific reductions of heparan sulfate and secondary storage biomarkers in Sanfilippo syndrome type A patients treated with the investigational gene therapy LYS-SAF302
1:12	Maria J. de Castro Hospital Clínico Universitario de Santiago de Compostela Santiago de Compostela, Spain	Updated results of Transpher B, a multicenter, single-dose, phase 1/2 clinical trial of ABO-101 gene therapy for Sanfilippo syndrome type B (MPS IIIB)
1:24	Anna I. Bakardjiev Denali Therapeutics South San Francisco, CA, United States	Intravenous ETV:IDS (DNL310) significantly reduces cerebrospinal fluid heparan sulfate in an open label Ph1/2 study in MPS II patients
1:36	Elizabeth M. Berry-Kravis Rush University Medical Center Chicago, IL, United States	Evidence for long-term efficacy of intrathecal adrabetadex for the treatment of neurological decline in patients with Niemann-Pick disease, type C1
1:48	Live Moderated Q&A	Michaël Hocquemiller, Maria de Castro, Anna Bakardjiev, and Elizabeth Berry-Kravis
2:00	Break & Exhibits
2:30	Poster Session
3:30	Virtual Networking Event

2021 ePoster Session Abstracts

This year over 330 scientific abstracts presented at five separate poster sessions. These sessions were an excellent opportunity to see, hear and discuss specific research topics directly with the abstract authors. Although the ePoster content was available throughout WORLDSymposium, the opportunity for live Q&A with the presenters were limited to their assigned date and time.

Click here to download the 2021 poster listing.

Any poster numbers not listed did not present as the author is unable to attend the conference.

All abstracts received by the October 1, 2020 deadline were considered for platform presentation and inclusion in the lysosomes issue of Molecular Genetics and Metabolism (MGM) which was published in February 2021. Poster notifications and assigned poster numbers were sent to the first author of the submitted abstract at the beginning of December, 2020.

Late-breaking abstract submission was open on November 1 and closed on December 1, 2020 for poster and possible platform presentation. A new featured session, Late-Breaking Science Friday, was added to the 2021 Scientific Program to highlight recent advances in lysosomal disease research. Selected abstracts from the Late-Breaking submission cycle was awarded an oral presentation time on Late-Breaking Science Friday. Due to publication deadlines, late-breaking abstracts were published in the virtual program materials, and were not published in Molecular Genetics and Metabolism (MGM).

Registered attendees had access to an electronic copy of the program and abstracts via the WORLDSymposium 2021 virtual platform. Registered attendees must login to the virtual platform using the confirmation code they received with their invitation to the virtual platform. The program and abstracts were copyrighted and were available to non-registrants through Elsevier.

It is the policy of WORLDSymposium to publish all abstracts with the list of authors exactly as the abstract was submitted to WORLDSymposium. The first author of the submitted abstract will be listed as the presenting author on the Preliminary Program, Agenda, and Poster List.

2021: Posters were Divided into Five (5) Separate Sessions

Authors who accepted an ePoster presentation were assigned to present their abstract live during one of five ePoster sessions, based on the final abstract category for each abstract. The ePosters opened at 2:30pm EST on Monday, February 8, 2021, and remained open throughout WORLDSymposium 2021.

All ePosters were located in the Virtual Exhibit & ePoster Hall:

Basic Science Abstracts was presented on Monday, February 8 from 2:30-3:30pm EST
Translational Research Abstracts was presented on Tuesday, February 9 from 2:30-3:30pm EST
COVID-19 and Clinical Trials Abstracts was presented on Wednesday, February 10 from 2:30-3:30pm EST
Contemporary Forum Abstracts was presented on Thursday, February 11 from 2:30-3:30pm EST
Late-Breaking Abstracts was presented on Friday, February 12 from 2:30-3:30pm EST

Any poster numbers not listed did not present as the author was unable to attend the conference.

ePosters were on the Virtual Platform and in the Mobile App

In addition, all poster presenters were required to submit an electronic version of their poster to be available to attendees throughout WORLDSymposium 2021.

Details on ePoster submission were sent to all first authors.

All registered attendees had access to the ePosters on the WORLDSymposium virtual platform. The ePosters are available to registered attendees through March 15, 2021.

2021 PATIENT ADVOCATE SHOWCASE

Batten Disease Support and Research Association

Cure GM 1 Foundation

The CURE GM1 FOUNDATION’s mission is to fund research for the benefit of all those who suffer from GM1 gangliosidosis. This nonprofit organization was founded by parents of children who suffer from GM1 who seek to save the lives of all those who suffer from this wretched condition. The Cure GM1 Foundation is dedicated to directly funding research for a cure for GM1 gangliosidosis – a lysosomal storage disease that attacks the brain and spinal cord, and is always fatal in children. GM1 is a progressive and degenerative condition with an extremely broad and debilitating array of symptoms and complications.

Cure Sanfilippo Foundation

Cure Sanfilippo Foundation is a 501c3 nonprofit who advocates, collaborates, and funds innovative and breakthrough research to ensure multiple promising paths are being explored for Sanfilippo Syndrome, in the effort to save children and better their quality of life. In addition to funding additional clinical trials, the Foundation has a focus on: 1) working with the FDA and biotechs regarding appropriate clinical trial endpoints and ensuring the caregiver voice is being incorporated every step of the way; 2) earlier diagnosis, diagnostic testing, and newborn screening; and 3) providing guidance and support to families who are navigating the landscape of clinical trials, insurance and physician support.

Fabry International Network

National MPS Society

United MSD Foundation

The United MSD Foundation was established to cure Multiple Sulfatase Deficiency (MSD), an ultra-rare lysosomal storage disorder that typically claims the lives of children before they are ten years old. With a promising Gene Therapy approach, our organization is raising the necessary funds for the first-ever MSD Phase One Clinical Trial.

2021 DIAMOND EXHIBITORS

Amicus Therapeutics

BioMarin Pharmaceutical Inc.

BioMarin is a world leader in developing and commercializing innovative therapies for rare diseases driven by genetic causes. With a 20-year history, BioMarin remains steadfast to its original mission—to bring new treatments to market that will make a big impact on small patient populations. These conditions are often inherited, difficult to diagnose, progressively debilitating, have few, if any, treatment options, and are usually ignored.

Sanofi Genzyme

Takeda Pharmaceuticals

Takeda is a patient-focused, values-based, R&D-driven global biopharmaceutical company; our passion and pursuit of potentially life-changing treatments are rooted in our history. We know patients with rare diseases have spent their lives overcoming challenges. That’s why for 30+ years we’ve been working to support them in their fight.

2021 PLATINUM EXHIBITORS

Audentes Therapeutics, an Astellas Company

Audentes Therapeutics, an Astellas company, is developing genetic medicines for life-threatening diseases. We are committed to bringing transformative treatments to patients living with serious, rare neuromuscular conditions as rapidly as possible. Audentes serves as the Astellas Center of Excellence for adeno-associated viruses (AAV) based genetic therapies. Our investigational therapies target rare diseases through three modalities: gene replacement, exon skipping gene therapy and vectorized RNA knockdown.

Chiesi Global Rare Diseases

Chiesi Global Rare Diseases is a business unit of the Chiesi Group established in February 2020 and focused on research and development of treatments for rare and ultra-rare disorders. The Global Rare Diseases unit works in collaboration with Chiesi Group to harness the full resources and capabilities of our global network to bring innovative new treatment options to people living with rare diseases, many of whom have limited or no treatments available. The unit is also a dedicated partner with global leaders in patient advocacy, research and patient care.

Orphazyme

Orphazyme is pioneering the Heat-Shock Protein response to develop innovative therapies for neurodegenerative orphan diseases. Arimoclomol, our lead candidate, is in development for four diseases: Niemann-Pick disease Type C (NPC), Gaucher Disease, Inclusion Body Myositis (IBM), and Amyotrophic Lateral Sclerosis (ALS).

2021 GOLD EXHIBITORS

Orchard Therapeutics

Orchard Therapeutics transforms the lives of patients with rare diseases through innovative gene therapies.

Spark Therapeutics

Ultragenyx Pharmaceutical Inc.

Ultragenyx is a biopharmaceutical company committed to bringing to patients novel products for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

2021 EXHIBITORS

AskBio

At Asklepios BioPharmaceutical (AskBio), we are making history with every clinical advancement and aspire to turn hope into cures by unraveling new possibilities for genetic medicine. We are headquartered in Research Triangle Park, North Carolina, a thriving biotechnology hub with nearly 600 life science companies, and have additional research and development facilities in Edinburgh, Scotland, and Paris, France, and gene therapy manufacturing in San Sebastian, Spain.

CENTOGENE GmbH

CENTOGENE is the global rare disease company − passionately transforming clinical, genetic, and multiomic data into medical insights. Founded in Germany, with U.S. headquarters in Boston-Cambridge/MA and operations around the world, CENTOGENE constantly delivers the broadest portfolio of cutting-edge platforms for human genetics solutions.

Denali Therapeutics

Denali Therapeutics Inc. is a biotechnology company developing drug candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases. We are committed to advancing new potential treatments for lysosomal disorders that affect the brain, starting with DNL310, our investigational IV enzyme replacement for Hunter syndrome.

Freeline

Freeline is a clinical-stage, fully integrated, next generation, systemic AAV-based gene therapy company with the ambition of transforming the lives of patients suffering from inherited systemic debilitating diseases.

Forge Biologics

Forge is a hybrid gene therapy company advancing an AAV pipeline and providing CDMO manufacturing. Forge’s lead program, FBX-101 is an AAV gene therapy for Krabbe disease. FBX-101 will be entering clinical trials in 2021.

Homology Medicines, Inc.

Homology Medicines, Inc. (NASDAQ: FIXX) is a clinical-stage genetic medicines company harnessing its broad and proprietary dual in vivo gene therapy and nuclease-free gene editing platform into potential one-time treatments for the rare disease community.

Idorsia Pharmaceuticals Ltd

The purpose of Idorsia is to discover, develop and bring more, innovative medicines to patients. We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into one of Europe’s leading biopharmaceutical companies, with a strong scientific core. Located near Basel, Switzerland – a bona fide European biotech hub – Idorsia is specialized in the discovery and development of small molecules to provide innovative therapeutic possibilities.

Invitae

JCR Pharmaceuticals Co., Ltd.

JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is redefining expectations and expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 45-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by leveraging our expertise in manufacturing and R&D to advance medicine. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients.Together we soar.

Passage Bio

At Passage Bio, we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with unparalleled access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies.

Pfizer

Pfizer Inc.: Working together for a healthier world^®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.comand follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

QPS Austria GmbH

Sigilon Therapeutics

Travere Therapeutics

Travere Therapeutics is a biopharmaceutical company dedicated to identifying, developing and delivering life-changing therapies to people living with rare disease.