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

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

8:45Chester 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
9:00Ellen Sidransky
National Human Genome Research Institute at National Institutes of Health (NIH)
Bethesda, MD, United States
Innovation Award Speaker Presentation
9:30Wei 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
9:42Shih-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
9:54Chester B. Whitley
University of Minnesota
Minneapolis, MN, United States
Immunogenicity, genotoxicity, and efficacy of PS gene editing in treating MPS I mice
10:06Lalitha 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
10:18Live Moderated Q&AWei Zhu, Shih-hsin Kan, Chester B. Whitley, and Lalitha Belur
10:30Break & Exhibits 
11:00Tyler 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
11:12Laura López de Frutos
Instituto de Investigación Sanitaria Aragón (IIS Aragón)
Zaragoza,Spain
Testing new biomarkers for lysosomal diseases
11:24Ying 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
11:36Paula Rozenfeld
Universidad Nacional de La Plata-CONICET, IIFP
La Plata,Argentina
Gaucher disease mesenchymal stem cells showed reduced osteogenesis and increased osteoclastogenesis and adipogenesis
11:48Live Moderated Q&ATyler Harm, Laura López de Frutos, Yin Sun, and Paula Rozenfeld
12:00Break, Exhibits and Satellite Symposia 
1:00Allen 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
1:12Behzad 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
1:24Dau-Ming Niu
Taipei Veterans General Hospital
Taipei,Taiwan
Development of a gene therapy for Fabry disease using adeno-associated viral vector mediated gene editing
1:36Stephanie 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
1:48Live Moderated Q&AAllen Seylani, Behzad Najafian, Dau-Ming Niu, and Stephanie Newman
2:00Break & Exhibits 
2:30Poster Session 
3:30Break, Exhibits and Networking 
4:00Satellite 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

9:00Chester B. Whitley
University of Minnesota
Minneapolis, MN, United States
2021 Patient Advocate Leader (PAL) Award Announcement and Presentation to Terri L. Klein
9:15Chester B. Whitley
University of Minnesota
Minneapolis, MN, United States
2021 Young Investigator Awards Announcement and Presentation
9:30Xin 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
9:42Rachel 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
9:54Li Ou
University of Minnesota
Minneapolis, MN, United States
PS gene editing with a novel HEXO construct to treat both Tay-Sachs and Sandhoff diseases
10:06Su 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
10:18Live Moderated Q&AXin Chen, Rachel Bailey, Li Ou, and Su Jin Choi
10:30Break & Exhibits 
11:00Troy Lund
University of Minnesota
Minneapolis, MN, United States
Biochemical predictors of neurocognitive outcomes in Hurler syndrome
11:12Jane 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
11:24Bernhard Gentner
San Raffaele Telethon Institute for Gene Therapy
Milano, Italy
Ex vivo hematopoietic stem cell gene therapy for mucopolysaccharidosis type I (Hurler syndrome)
11:36Bryan Pukenas
University of Pennsylvania
Philadelphia, PA, United States
Intracisternal administration of AAV9 gene therapies to target the central nervous system
11:48Live Moderated Q&ATroy Lund, Jane Kinsella, Bernhard Gentner, and Bryan Pukenas
12:00Break, Exhibits and Satellite Symposia 
1:00John Day
Stanford University
Stanford, CA, United States
A phase I/II open-label gene replacement clinical study for late onset Pompe Disease
1:12Torayuki 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
1:24Julian 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
1:36Calogera 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
1:48Live Moderated Q&AJohn Day, Torayuki Okuyama, Julian Raiman, and Calogera Simonaro
2:00Break & Exhibits 
2:30Poster Session 
3:30Break, Exhibits & Networking 
4:00Satellite 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

8:55Chester B. Whitley
University of Minnesota
Minneapolis, MN, United States
Welcome and Keynote Speaker Introduction
9:00Michael T. Osterholm
University of Minnesota
Minneapolis, MN, United States
Keynote Address:The COVID Pandemic: The Evolving Reality
9:30Live Moderated Q&AMichael T. Osterholm
9:45Heather 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
9:57Matheus 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
10:09Siddhee Sahasrabudhe
University of Minnesota
Minneapolis, MN, United States
Modeling potential interactions between oral Gaucher disease treatment and investigational COVID-19 therapies
10:21Live Moderated Q&AHeather Lau, Matheus Wilke, and Siddhee Sahasrabudhe
10:30Break & Exhibits 
11:00George 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
11:12Nicole Muschol
UKE – Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Tralesinidase alfa (AX 250) enzyme replacement therapy for Sanfilippo syndrome type B
11:24Emily 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
11:36Francesca 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
11:48Live Moderated Q&AGeorge Diaz, Nicole Muschol, Emily de los Reyes, and Francesca Fumagalli
12:00Break, Exhibits and Satellite Symposia 
1:00Ankit 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
1:12Melissa 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
1:24Ales 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
1:36Raphael 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
1:48Live Moderated Q&AAnkit Desai, Melissa Wasserstein, Ales Linhart, and Raphael Schiffmann
2:00Break & Exhibits 
2:30Poster Session 
3:30Break, Exhibits & Networking 
4:00Satellite 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

8:45Chester B. Whitley
University of Minnesota
Minneapolis, MN, United States
Welcome and Keynote Address Introduction
8:50Peter 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
9:20Live Moderated Q&APeter Marks
 The following session is not available for CME/CE accreditation (unless noted otherwise); CEU credits for GCs may apply.
9:30Jeffrey Alexander
Spark Therapeutics, Inc
Philadelphia, PA, United States
IdeS: An enabling technology to overcome the limitation of neutralizing antibodies to AAV gene therapy
9:42Marie-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
9:54Drew Tietz
Sigilon Therapeutics
Cambridge, MA, United States
SIG-018: Novel encapsulated non-viral cell-based therapy for MPS II
10:06Annie 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
10:18Live Moderated Q&AJeffery Alexander, Marie-Laure Nevoret, Drew Tietz, and Annie Arguello
10:30Break & Exhibits 
11:00Niek van Til
AVROBIO
Cambridge, MA, United States
Long-term hematopoietic stem cell gene therapy corrects neuromuscular manifestations in preclinical study of Pompe mice
11:12Rachel Botham
Codexis
Redwood City, CA, United States
Engineering α-glucosidase to improve protein stability and cellular uptake for the potential treatment of Pompe disease
11:24Dustin Armstrong
Valerion Therapeutics
Concord, MA, United States
VAL-1221: Treating Pompe disease via enhanced glycogen-targeting
11:36Romuald Corbau
Freeline
Stevenage, United Kingdom
FLT201: An AAV-mediated gene therapy for type 1 Gaucher disease designed to target difficult to reach tissues
11:48Live Moderated Q&ANiek van Til, Rachel Botham, Dustin Armstrong, and Romuald Carbau
12:00Break, Exhibits and Satellite Symposia 
1:00John 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
1:12Deborah 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
1:24Cristina 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
1:36Miganush Stepanians
PROMETRIKA, LLC
Cambridge, MA, United States
A survey of statistical study design and analysis methods for rare disease development programs
1:48Live Moderated Q&AJohn Jefferies, Deborah Marsden, Cristina Baricordi, and Miganush Stepanians
2:00Break & Exhibits 
2:30Poster Session 
3:30Break, Exhibits & Networking 
4:00Satellite 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.

9:30Cathal 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
9:42Jennifer Clarke Matthews
Sanofi
Framingham, MA, United States
Murine models of lysosomal diseases exhibit differences in brain protein aggregation and neuroinflammation
9:54Miles 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)
10:06Juana I. Navarrete
Hospital Central Sur PEMEX
Mexico City, Mexico
Use of biomarkers to follow up positive lysosomal diseases in newborn screening
10:16Benedikt 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.
10:24Live Moderated Q&ACathal Mahon, Jennifer Clarke Matthews, Miles Smith, Juana Navarrete and Benedikt Schoser
10:40Break & Exhibits 
11:00Stephanie 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
11:12Priya 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
11:24Mark 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
11:36Kevin 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)
11:48Live Moderated Q&AStephanie Cherqui, Priya Kishnani, Mark Thomas, and Kevin Flanigan
12:00Break, Exhibits and Satellite Symposia 
1:00Michaël 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
1:12Maria 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)
1:24Anna 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
1:36Elizabeth 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
1:48Live Moderated Q&AMichaël Hocquemiller, Maria de Castro, Anna Bakardjiev, and Elizabeth Berry-Kravis
2:00Break & Exhibits 
2:30Poster Session 
3:30Virtual Networking Event