WORLDSymposium™ 2021 Full Program on Lysosomal Diseases
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 |