WORLDSymposium 2015 Program

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. Whitley
University 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. Herbig
Immusoft
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