WORLDSymposium™ 2015 Full Program on Lysosomal Diseases
| 1:00 – 5:00 | Pre-Conference Symposium | Emerging Trends: State of the Art for Experts (Registration required) |
| 5:30 | Satellite Symposium Supported by PTC Therapeutics | New Strategies for MPS: A novel approach to address unmet needs in nonsense mutation MPS 1 |
Basic and bench research. Following the opening remarks, presentations in the morning and afternoon sessions will discuss 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. On Tuesday, the noon hour is reserved for a meeting with the WORLDSymposia Council of Patient Advocates (COPA)™ that focuses on patient involvement in research planning and subject recruitment.
Basic Science I
Co-Chairs: Perry Hackett & Jill Morris
| 6:45 | Satellite Symposium Supported by BioMarin Pharmaceutical Inc. | Emerging Issues in MPS: Management of Adult Patients |
| 7:50 | Chester B. WhitleyUniversity of Minnesota Minneapolis, MN, United States | Welcome and Opening Remarks |
| 8:00 | Steven C. Groft National Institute of Health Bethesda, MD, United States | WORLDSymposium 2015 Award for Innovation and Accomplishment |
| 8:30 | Sandra D.K. Kingma Academic Medical Center Amsterdam, Netherlands | A study on the influence of glycosaminoglycan and growth factor interaction in mucopolysaccharidosis type I bone disease |
| 8:45 | Richard Steet University of Georgia Athens, GA, United States | Small molecule modulation of CI-MPR-dependent uptake of therapeutic enzymes in patient fibroblasts |
| 9:00 | Alexey Pshezhetsky CHU Ste-Justine, University of Montreal Montreal, QC, Canada | Brain disease in mucopolysaccharidosis IIIC mouse: neuroinflammation, mitochondrial defects and neurodegeneration |
| 9:15 | Sun H. Peck University of Pennsylvania Philadelphia, PA, United States | Failed vertebral bone formation in mucopolysaccharidosis VII dogs is associated with impaired chondrocyte hypertrophic differentiation |
| 9:30 | Eric J. HerbigImmusoft Seattle, WA, United States | Sleeping Beauty engineered human B lymphocytes express therapeutic levels of human iduronidase: a new approach for mucopolysaccharidosis type I |
| 9:45 | Shaalee Dworski University of Toronto Toronto, ON, Canada | Spatial distribution of brain ceramides in an acid ceramidase deficient murine model: subsequent histological manifestations and functional deficits |
| 10:00 | Break & Exhibits | |
| 10:15 | Lishu Li NIAMS, National Institutes of Health Bethesda, MD, United States | Two masters of lysosomal and autophagosomal biogenesis, TFEB and TFE3, and their potential therapeutic value in Pompe disease |
| 10:30 | Fabian P.S. Yu University of Toronto Toronto, ON, Canada | Impaired lung function in the acid ceramidase deficient mouse |
| 10:45 | Matilda R. Jackson University of Adelaide Adelaide, Australia | α-L-iduronidase transduced mesenchymal stem cells improve the behavioural deficits in mucopolysaccharidosis type I mice |
| 11:00 | Daniel K. Borger National Institutes of Health Bethesda, MD, United States | Impaired autophagy leads to inflammasome activation and a heightened inflammatory profile of macrophages in Gaucher disease |
| 11:15 | Derek G. Burke Institute of Child Health, University College London London, United Kingdom | Lysosomal β-glucosidase (GBA1) and non-lysosomal β-glucosidase (GBA2), potential involvement in the pathogenesis of Gaucher disease/Parkinson disease |
| 11:30 | Lunch Break | Council of Patient Advocates (COPA) or Lunch On Your Own |
Basic Science II
Co-Chairs: Rashmi Gopal-Srivastava & Scott McIvor
| 1:00 | Keisuke Kitakaze The University of Tokushima Tokushima, Japan | Development of protease−resistant modified human β-hexosaminidase B and evaluation of intracerebroventricular replacement effects on GM2 gangliosidosis model mice |
| 1:15 | Nilima Kolli University of Massachusetts Amherst Amherst, MA, United States | Molecular basis of sialidosis and its treatment |
| 1:30 | Hitoshi Sakuraba Meiji Pharmaceutical University Kiyose, Japan | Determination of the structure of human α-l-iduronidase and structural basis of mucopolysaccharidosis type Ι |
| 1:45 | Takahiro Tsukimura Meiji Pharmaceutical University Kiyose, Japan | Comprehensive study of Fabry disease: gene mutation, GLA activity, GLA protein and globotriaosylsphingosine |
| 2:00 | Sheng Dai National Institutes of Health Bethesda, MD, United States | Rapid kinetics of beta-cyclodextrin entering and exiting cells: implication of its mechanism on reduction of cholesterol accumulation in Niemann-Pick disease type C cells |
| 2:15 | Robert J. Desnick Mount Sinai School of Medicine New York, NY, USA | Fabry disease: the α-galactosidase A (GLA) c.427G>A (A143T) mutation, effect of the 5′-10C>T polymorphism |
| 2:30 | Janine Reunert University Hospital Muenster Muenster, Germany | Improved diagnostics of Niemann-Pick type C by the analysis of plasma oxysterols |
| 2:45 | Break & Exhibits | |
| 3:00 | Camilla Tøndel Haukeland University Hospital Bergen, Norway | Foot process effacement is an early marker of nephropathy in young classic Fabry patients without albuminuria |
| 3:15 | Francyne Kubaski University of Delaware Newark, DE, United States | Noninvasive pulmonary function test on Morquio syndrome type A patients |
| 3:30 | Jorge J. Cebolla Hospital Universitario Miguel Servet Zaragoza, Spain | Experience with 7-ketocholesterol and ccl18/parc as surrogated biomarkers in a series of Spanish Niemann-Pick disease type C patients |
| 3:45 | Janine Gilkes University of Florida Gainesville, FL, United States | Evaluation of biodistribution and transduction profiles of novel AAV8 capsid mutated variants as a therapeutic candidate for the treatment of MPS IIIB |
| 4:00 | John J. Naleway Marker Gene Technologies, Inc. Eugene, OR, United States | Targeted chaperone therapy agents for Gaucher disease |
| 4:15 | Robert R. Gotschall Amicus Therapeutics Cranberry, NJ, United States | Novel recombinant human acid α-glucosidase with optimal glycosylation is significantly better than standard of care enzyme replacement for glycogen clearance in skeletal muscles of GAA knock-out mice |
| 4:30 | Poster Reception & Presentation | |
| 6:30 | Satellite Symposium Supported by Amicus Therapeutics | Next Generation for Lysosomal Disorders: Treatments, Biomarkers and Talent Needed to Succeed |
Translational research. The second day of the meeting turns to the challenge of moving laboratory discoveries to therapy, the important hurdles of translational research. Some broad topics of discussion include modulation of CNS affects of disease, how to increase the efficacy of therapeutic modalities, and genotype/phenotype correlations.
Translational Research I
Co-Chairs: David Pearce & Danilo Tagle
| 6:45 | Satellite Symposium Supported by Shire | Discovery and Research Platforms in Rare Disease |
| 7:50 | Chester B. Whitley University of Minnesota Minneapolis, MN, United States | Welcome and Opening Remarks |
| 8:00 | Laurie Muldowney, Keynote Speaker Division of Gastroenterology and Inborn Error Products CDER/FDA Silver Spring, MD, United States | The importance of natural history studies and patient focused data in drug development |
| 8:30 | C. Ronald Scott University of Washington Seattle, WA, United States | Identification of newborn infants at risk for a lysosomal disease by tandem mass spectrometry |
| 8:45 | Andrea M. Atherton Children’s Mercy Hospital Kansas City, MO, United States | The first two years of full population pilot newborn screening for lysosomal disorders: the Missouri experience |
| 9:00 | Edward H. Schuchman Icahn School of Medicine at Mount Sinai New York, NY, United States | Novel use of the lysosomal enzyme acid ceramidase for the treatment of inflammatory lung diseases, including cystic fibrosis |
| 9:15 | Wendy E. Heywood University College London London, United Kingdom | Urine biomarker discovery using label free proteomics reveals novel markers for the monitoring of treatment for mucopolysaccharide disorders |
| 9:30 | David M. Bedwell UAB Birmingham, AL, United States | The nonsense suppression drug PTC124 restored alpha-l-iduronidase activity and reduces glycosaminoglycan accumulation in MPS IH mice carrying the Idua-W402X mutation |
| 9:45 | Calogera M. Simonaro Icahn School of Medicine at Mount Sinai New York, NY, United States | Pentosan polysulfate: new mechanistic insights and treatment of the mucopolysaccharidoses |
| 10:00 | Break & Exhibits | |
| 10:15 | Suresh Vijay Birmingham Children’s Hospital Birmingham, United Kingdom | Evaluation of blood-brain barrier integrity and structural abnormalities in MPS IIIb patients using cerebrospinal fluid/serum albumin index (CSF-AI) and multimodal MRI |
| 10:30 | Jean E. Lachowicz Angiochem Montreal, QC, Canada | Systemic administration of a brain-penetrant peptide-iduronidase conjugate results in brain IDUA activity in MPS I mice |
| 10:45 | Jeffrey Esko University of California, San Diego La Jolla, CA, United States | Intranasal enzyme replacement therapy in mice |
| 11:00 | Eun-Young Choi NICHD/NIH Bethesda, MD, United States | Choroid plexus-directed viral gene therapy for α-mannosidosis, a prototypical lysosomal disease |
| 11:15 | Russell DeKelver Sangamo BioSciences Richmond, CA, United States | ZFN-mediated genome editing of albumin “safe harbor” in vivo results in supraphysiological levels of human IDS, IDUA and GBA in mice |
| 11:30 | Lunch Break | Toolkit: Patient Reported Outcomes and Measures of Disease Severity in Lysosomal Disease (Registration required) or Lunch On Your Own |
Translational Research II
Co-Chairs: Walter Low & Ellen Sidransky
| 1:00 | James M. Wilson University of Pennsylvania Perelman School of Medicine Philadelphia, PA, United States | Adeno-associated virus vector-mediated gene therapy can effectively treat CNS and cardiac lesions and induce immune tolerance to the therapeutic enzyme in large animal models of mucopolysaccharidosis type I |
| 1:15 | Stuart M. Ellison University of Manchester Manchester, United Kingdom | Pre-clinical workup of lentiviral mediated stem cell gene therapy for mucopolysaccharidosis type IIIA |
| 1:30 | Claire O’Leary University of Manchester Manchester, United Kingdom | Development of an adeno-associated viral vector for mucopolysaccharidosis IIIC |
| 1:45 | Katherine Ponder Washington University School of Medicine St. Louis, MO, United States | Intrathecal injection of lentiviral vector results in high expression in the brain of mucopolysaccharidosis VII dogs but the pattern of expression is different than for AAV9 or AAV-rh10 |
| 2:00 | Jeff Peng BioMarin Pharmaceutical Inc. Novato, CA, United States | Improved respiratory function in a mouse model of Pompe disease treated with BMN 701 |
| 2:15 | Nicholas P. Clayton Genzyme, a Sanofi company Framingham, MA, United States | Antisense oligonucleotide-mediated suppression of muscle glycogen synthase 1 synthesis as an approach for substrate reduction therapy of Pompe disease |
| 2:30 | Adeel Safdar McMaster University Hamilton, ON, Canada | Therapeutic potential of exosomoes in Pompe disease: treatment of tomorrow, today for lysosomal diseases |
| 2:45 | Break & Exhibits | |
| 3:00 | Marcio M. Andrade-Campos IACS Zaragoza, Spain | Multiple myeloma and Gaucher disease share features of a cytokine profile |
| 3:15 | John Marshall Genzyme, a Sanofi company Framingham, MA, United States | Evaluation of a novel substrate reduction therapy with CNS access in mouse models of neuronopathic Gaucher disease |
| 3:30 | Matthew Nguyen National Institutes of Health Bethesda, MD, United States | Development of a novel neuronal cell model for investigating the link between glucocerebrosidase and Parkinson disease |
| 3:45 | Ashley N. Gonzalez National Institutes of Health Bethesda, MD, United States | Modeling the association between Gaucher disease and Parkinson disease using in vivo mouse models |
| 4:00 | Charles H. Vite University of Pennsylvania Philadelphia, PA, United States | Intracisternal cyclodextrin ameliorates neurological dysfunction, increases survival time, and stops Purkinje cell death in feline Niemann-Pick disease type C1 |
| 4:15 | Suhail Alam University of Notre Dame Notre Dame, IN, United States | A new formulation for the treatment of neurological and systemic defects in Niemann-Pick disease type C |
| 4:30 | Poster Reception & Presentation | |
| 6:45 | Satellite Symposium Supported by Genzyme, a Sanofi company | Advancing the Management of Gaucher’s Disease |
Clinical research. The entire third day is committed to presentations of results from clinical trials, in most cases, the actual application of new agents in humans affected by these conditions. Day 3 will also include presentations related to re-thinking the definition of biomarkers for lysosomal disease.
Clinical Trials I
Co-Chairs: James Cloyd & Elsa Shapiro
| 6:45 | Satellite Symposium Supported by BioMarin Pharmaceutical Inc. | The Impact of Late Onset Pompe Disease on Respiratory Function |
| 7:50 | Chester B. Whitley University of Minnesota Minneapolis, MN, United States | Welcome and Opening Remarks |
| 8:00 | Jenny Kim National Institutes of Health Bethesda, MD, United States | Gaucher disease and Parkinsonism: clinical course and prognosis |
| 8:15 | Timothy M. Cox Department of Medicine, Addenbrooke’s Hospital Cambridge, United Kingdom | ENCORE, a randomized, controlled, open-label non-inferiority study comparing eliglustat to imiglucerase in Gaucher disease type 1 patients stabilized on enzyme replacement therapy: 24-month results |
| 8:30 | Pramod Mistry Yale University New Haven, CT, United States | ENGAGE, a phase 3, randomized, double-blind, placebo-controlled, multi-center study to investigate the efficacy and safety of eliglustat in adults with Gaucher disease type 1: results after 18 months |
| 8:45 | Sandrine Turpault Genzyme, a Sanofi company Cambridge, MA, United States | CYP2D6 phenotype-based dosing of eliglustat |
| 9:00 | Ari Zimran Gaucher Clinic, Shaare Zedek Medical Center and the Hadassah Medical School-Hebrew University Jerusalem, Israel | Long-term safety and efficacy of taliglucerase alfa in pediatric patients with Gaucher disease who were treatment-naïve previously treated with immiglucerase |
| 9:15 | Marieke Biegstraaten Academic Medical Center Amsterdam, Netherlands | Consensus recommendations on initiation and cessation of enzyme replacement therapy in patients with Fabry disease |
| 9:30 | Robert J. Hopkin Cincinnati Children’s Hospital Medical Center Cincinnati, OH, United States | Risk factors for severe clinical events and the incidence of these events in male and female patients with Fabry disease treated with agalsidase beta |
| 9:45 | Derralynn Hughes University College London London, United Kingdom | Long-term efficacy and safety of migalastat compared to enzyme replacement therapy in Fabry disease: phase 3 study results |
| 10:00 | Break & Exhibits | |
| 10:15 | Dominique P. Germain University of Versailles Montigny, France | A 10-year study documenting the long-term effectiveness of agalsidase-beta treatment in 52 adult patients with classic Fabry disease |
| 10:30 | Raphael Schiffmann Baylor Research Institute Dallas, TX, United States | A prospective 10 year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease |
| 10:45 | Einat Almon Protalix Carmiel, Israel | Novel treatment for Fabry disease, IV administration of plant derived α-GAL-A enzyme phase 1/2 safety and efficacy study: interim clinical report |
| 11:00 | Joseph Muenzer University of North Carolina Chapel Hill Chapel Hill, NC, United States | Long-term biomarker and cognitive follow up of children with Hunter syndrome receiving intrathecal enzyme replacement therapy |
| 11:15 | Paul Harmatz UCSF Benioff Children’s Hospital Oakland Oakland, CA, United States | Impact of elosulfase alfa on pain in patients with Morquio syndrome type A |
| 11:30 | Lunch Break | Council of Industry Leaders (COIL) or Lunch On Your Own |
Clinical Trials II
Co-Chairs: Agnes Chen & Raphael Schiffmann
| 1:00 | Igor Nestrasil University of Minnesota Minneapolis, MN, United States | Brain volumes and cognitive function in MPS IIIB (Sanfilippo syndrome type B): cross-sectional study |
| 1:15 | Samantha Parker Lysogene Paris, France | AAVrh10-SGSH intracerebral gene therapy corrects the defect and improves the health status in mucopolysaccharidosis type IIIA |
| 1:30 | Julie B. Eisengart University of Minnesota Minneapolis, MN, United States | Clinical outcomes of Hurler syndrome treated exclusively with enzyme replacement therapy from a young age |
| 1:45 | Simon A. Jones St Mary’s Hospital, CMFT, University of Manchester Manchester, United Kingdom | Enzyme replacement therapy (ERT) for mucopolysaccharidosis VII (MPS VII; Sly syndrome) reduces lysosomal storage in a 36-week phase 1/2 clinical study |
| 2:00 | Raymond Y. Wang University of California, San Diego La Jolla, CA, United States | Carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult populations |
| 2:15 | Arunabha Ghosh Willink Biochemical Genetics Unit Manchester, United Kingdom | Use of enzyme replacement therapy prior to haematopoietic stem cell transplantation for severe mucopolysaccharidosis I, a 10 year, 2-centre retrospective review |
| 2:30 | Paul McIntosh Duke University Medical Center Durham, NC, United States | Characterization of gait in late onset Pompe disease |
| 2:45 | Break | |
| 3:00 | Priya S. Kishnani Duke University Medical Center Durham, NC, United States | Prophylactic immune modulation in infantile Pompe disease; collective experience treating CRIM-positive and negative patients in the naïve setting |
| 3:15 | Beth L. Thurberg Genzyme, a Sanofi company Cambridge, MA, United States | A phase 4 prospective study in patients with adult Pompe disease treated with alglucosidase alfa |
| 3:30 | Barbara Burton, on behalf of the ARISE Investigators Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children’s Hospital Chicago, IL, United States | Results of a global phase 3, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of sebelipase alfa as an enzyme replacement therapy in children and adults with lysosomal acid lipase deficiency |
| 3:45 | Simon A. Jones Manchester Centre for Genomic Medicine, CMFT, University of Manchester Manchester, United Kingdom | Effect of sebelipase alfa on survival and liver function in infants with rapidly progressive lysosomal acid lipase deficiency |
| 4:00 | Melissa P. Wasserstein Icahn School of Medicine at Mount Sinai New York, NY, United States | An open-label, multicenter, ascending-repeat-dose study of the tolerability and safety of recombinant human acid sphingomyelinase (rhASM) in patients with ASM deficiency (ASMD) |
| 4:15 | Jonathan P. Dyke Weill Cornell Medical College New York, NY, United States | Comparison of cortical thinning in late infantile neuronal ceroid lipofuscinosis with a normative pediatric population using magnetic resonance imaging |
| 6:00 | Closing Banquet and Award Ceremony | New Treatment Awards |