Towards Clinical Progress in the Mucopolysaccharidoses

Towards Clinical Progress in the Mucopolysaccharidoses

Washington Plaza Hotel
Washington, D.C.
March 7-8, 2007

Overview
The National Institute of Neurological Disorders and Stroke (NINDS), the Office of Rare Diseases (ORD), and the National Institute of Diabetes and Digestive and Kidney Diseases at NIH along with the National MPS Society co-sponsored this workshop. This scientific workshop was organized by Mark Haskins, V.M.D., Ph.D. (University of Pennsylvania); Sissi Langford (National MPS Society); Catherine McKeon, Ph.D. (National Institute of Diabetes and Digestive and Kidney Diseases); Mark Sands, Ph.D. (Washington University School of Medicine); and Danilo A. Tagle, Ph.D. (National Institute of Neurological Disorders and Stroke)

The goals of the workshop include:

• The goal of this workshop is to identify and address impediments to effective therapies in the mucopolysaccharidoses (MPS)
• To develop a strategy to determine the minimum standard protocol for clinical application of effective therapies for MPS and other lysosomal storage disorders (LSDs).

Executive Summary
There was considerable progress reported at this workshop on both the clinical and basic research areas in the mucopolysaccharidoses (see agenda). The Panel Discussions also identified areas of research that are required for efficient translation of new therapies and approaches into the clinic.

Progress in basic and translational research:

A) Enzyme Replacement:
William Sly presented preliminary data showing that completely de-glycoslyated -glucuronidase had a dramatically increased half-life in serum and virtually eliminated lysosomal storage in the CNS of adult MPS VII mice. This surprising finding has obvious and important implications for the treatment of the CNS disease associated with MPS disorders.

Elizabeth Neufeld presented the principles behind the development of aptamer-based modifications of recombinant α-L-iduronidase for treatment of the CNS disease associated with MPS I. Preliminary data generated in an in vitro blood brain barrier model shows that this approach may be able to deliver enzyme across the blood-brain barrier (BBB).

Patricia Dickson showed promising data using intrathecal delivery of α-L-iduronidase in the canine model of MPS I. The levels of glycosaminoglycans in the brain were normalized and the enzyme persisted for 4-7 days.

B) Small Molecule Therapy:
Thomas Seyfried showed that treatment with NB-DGJ, which interferes with the synthesis of gangliosides, decreased the levels of gangliosides in the mouse models of GM1 gangliosidosis and Sandhoff disease. In addition, he showed that caloric restriction decreased inflammation, improved rotarod performance, and increased the life span of these mice, however, there was no reduction in gangliosides. Experiments are ongoing to determine the efficacy of combining substrate reduction and dietary restriction.

Steven Walkley showed that substrate reduction and by-product replacement therapies were partially effective in Niemann-Pick type C disease. He also showed that combining the two approaches was more effective than either therapy alone.

Frances Platt studied the effects of small molecule substrate reduction therapy combined with bone marrow transplantation, neuronal stem cells, or non-steroidal anti-inflammatory drugs. Each therapeutic approach synergized with substrate reduction therapy to varying degrees.

David Bedwell developed a murine model that contained an authentic human non-sense mutation leading to MPS I. Using this model he was able to test a safer (less toxic) analog of gentamycin for stop codon read-through. This safer drug was able to restore approximately 3% of the enzyme activity in vitro and reduced urinary glycoaminoglycans (GAGs) in vivo.

C) Stem Cells
Kyuson Yun showed that fetal liver cells cultured with Noggin resulted in a 5- fold increase in the generation of neuronal stem cells. Small numbers of these cells were seen in the brain following intracranial injection of transduced cells. Data was also presented describing an easily accessible source (nasal epithelium) of autologous neuronal stem cells that express the correct neuronal markers in vitro.

Raquel Walton presented in vitro data suggesting that there is a block in the maturation of neuronal stem cells derived from several different areas of the MPS VII dog brain. When transplanted into the brains of MPS VII dogs, only GUSB-positive astrocytes were observed and no GUSB-positive neurons were detected.

Nobuko Uchida presented pre-clinical data showing that human neuronal stem cells distributed widely throughout the neuraxis and reduced the clinical signs associated with the Shiverer mouse. The cells also distributed similarly throughout the brains in the mouse model of Infantile Batten Disease.

D) Gene Therapy:
Miguel Sena-Esteves showed that direct intracranial injection of either AAV1 or AAV8 reduced ganglioside and cholesterol accumulation in the brains of GM1 gangliosidosis mice. Retrograde transport of -galactosidase was observed with both vectors, and enzyme activity was observed as distant as the retina and spinal cord following AAV8 injection.

Gordon Watson showed that intrathecal injection of an AAV vector resulted in persistent expression and widespread reduction of lysosomal storage throughout the CNS in both the MPS VII and MPS I mouse models.

John Wolfe showed that intracranial injection of an AAV1 vector into the brain of -mannosidosis cats resulted in widespread correction of disease, and dramatic clinical improvement of the animals. He also showed that a 1 l injection of AAV in the ventral tegmental area, which sends projections to many areas of the brain, can deliver enzyme and reduce lysosomal storage throughout the brain in MPS VII mice.

Kathy Ponder extended her studies using retroviral-mediated gene therapy in newborn MPS I dogs and showed that in addition to correction in visceral organs, other tissues that have been refractory to conventional therapies (aorta and brain) also respond to high expression during the newborn period. Alberto Auricchio, using MPS VI rats and cats, showed that AAV1 and AAV8 expressing arylsulfatase B transduced the muscle and liver, respectively. He showed that each target tissue expressed high levels of enzyme but arylsulfatase B was not secreted from muscle. Data describing the clinical response is still pending.

Jay Dritz showed pre-clinical data comparing the levels of expression of GUSB and GUSB-TAT in the hematopoietic compartment following lentiviral mediated gene therapy. High level expression in multiple tissues was observed. Effects on critical tissues such as the brain and kidney are pending. Jean-Michel Heard showed that there was persistent and widespread expression of α-L-iduronidase in the brains of MPS I dogs following 8 separate injections of an AAV5 vector. Lysosomal storage was reduced in targeted areas of the brain. However, immunosuppression (cyclosporine) was required to maintain expression.

Matthew Ellinwood presented similar data in the canine model of MPS IIIB. Three affected but pre-symptomatic dogs were injected intracranially with an AAV5 vector and were maintained on an immunosuppressive regimen. There was widespread enzyme distribution and their neurological exam was normal at sacrifice, however, significant inflammatory lesions were seen in the absence of immunosuppression.

Xiucui Ma presented data showing that long term expression of α-L-iduronidase was possible in dogs with MPS I treated as young adults following transient treatment with anti-CD4 or anti-CD40 ligand combined with CTLA-4. Interestingly, data was also presented that showed improvements in skeletal disease, auditory-evoked brain stem responses, and decreased storage in the brain. Adarsh Reddy showed that bone marrow transplantation or CNS-directed AAV-mediated gene therapy alone in the murine model of globoid-cell leukodystrophy resulted in significant increases in life span to an average of 45 and 55 days of age, respectively. However, when combined the two disparate therapies synergized dramatically and resulted in an average life span of 105 days.

Mark Sands presented follow- up data on the original observation of hepatocellular carcinoma following systemic AAV-mediated gene therapy. They repeated the original observation in a larger cohort of animals and showed that all of the AAV proviral sequences integrated in a region of mouse chromosome 12 that contains a large number of microRNAs. These integration events disrupted the normal expression pattern in that region.

E) Animal Models:
Andrea Ballabio discussed the characterization of the multiple sulfatase deficiency mice. This mouse has a very severe phenotype which includes systemic inflammation, neurodegeneration, and a defect in autophagy.

Progress in clinical research:

A) Enzyme Replacement:
Three recombinant protein products are currently approved for clinical use for enzyme replacement therapy in MPS I (Aldurazyme), MPS II (Elaprase) and MPS VI (Naglazyme). In general, the clinical response following intravenous infusion has been positive with reduced hepatosplenomegaly, increased range of motion, increased stamina, and decreased urinary GAGs. Enzyme replacement products are in development for MPS IV and MPS VII.

Patricia Dickson discussed the preliminary findings of a human clinical trial to test the safety of intrathecal delivery of α-L-iduronidase. Three patients have been entered into the trial. So far the drug seems to be well tolerated with no severe adverse reactions and two patients have shown some symptomatic improvement.

B) Gene Therapy:
Ron Crystal discussed the preliminary data from an AAV2-mediated CNS-directed gene therapy clinical trial in children with Late Infantile Neuronal Ceroid Lipofuscinosis. So far, the procedure has been well tolerated and there is preliminary evidence that the procedure may be providing some efficacy. He also outlined improvements to the current protocol, specifically, the use of a new AAV serotype (rh from rhesus) that results in higher level expression and distribution in the brain. Jean-Michel Heard outlined an AAV5-mediated CNS-directed human gene therapy clinical trial for MPS I. This trial is based on the pre-clinical data generated in the canine model of MPS I.

C) Stem Cell-Mediated Therapy:
Nobuko Uchida presented preliminary data regarding a human clinical trial for Infantile Neuronal Ceroid Lipofuscinosis using neuronal stem cells. Several children have been injected and there have been no severe adverse reactions as of yet. Clinical evaluation is pending.

Joanne Kurtzberg discussed the use of umbilical cord blood for the treatment of lysosomal disorders. They have clear evidence that early treatment (as early as several weeks or months of age) is critical for effective therapy. They have also initiated a trial where they have added accessory cells that enhance early engraftment (data are pending).

D) Newborn Screening and developing Outcome Measures
Ronald Scott and John Hopwood gave updates on the progress with comprehensive newborn screening for lysosomal storage diseases. John Hopwood discussed his plans for screening 100,000 newborns in Australia with his mass spectrometry approach.

Joe Muenzer, Chet Whitley and Maria Escolar discussed the importance of meaningful clinical outcomes and natural history collection for the evaluation of various clinical trials.

Research Directions and Anticipated Needs:

The most important issues that the workshop participants expressed consist of 1) the need for natural history studies, 2) newborn screening programs, and 3) meaningful clinical outcome measures.

It is becoming clear that initiating therapy as early as possible is critical for the effective treatment of these diseases. This highlights the need for newborn screening and the collection of natural history data to move the novel therapies to the clinic.

There is growing evidence that combining various therapeutic modalities (small molecule, enzyme replacement, bone marrow transplantation, and gene therapy) can be synergistic and dramatically increase efficacy.

Over the last 5-10 years, the discussions have shifted from "how to treat these diseases" to "how do we get the therapies into the clinic". This is a very encouraging sign!

Towards Clinical Progress in the Mucopolysaccharidoses
Washington Plaza Hotel
Washington, D.C.
March 7-8, 2007

AGENDA

Workshop Objectives: To identify and address impediments to effective therapies, and to develop a strategy to determine the minimum standard protocol for clinical application of effective therapies for MPS and other LSDs

Organizers: Mark Haskins, V.M.D., Ph.D. (University of Pennsylvania); Sissi Langford (National MPS Society); Catherine McKeon, Ph.D. (National Institute of Diabetes and Digestive and Kidney Diseases); Mark S. Sands, Ph.D. (Washington University in St. Louis); and Danilo Tagle, Ph.D. (National Institute of Neurological Disorders and Stroke)

Tuesday	March 6
6:00 p.m.-8:00 p.m.	Early Registration/ Optional Open House, Sponsored by the National MPS Society
Wednesday	March 7
7:30 a.m.-8:00 a.m.	Registration/Continental Breakfast
8:00 a.m.-8:15 a.m.	Welcome/Introduction from Meeting Organizers Welcome from NINDS and ORD: Story C. Landis, Ph.D., and Stephen C. Groft, Pharm.D. Statement of Workshop Goals: Meeting Organizers
8:15 a.m.-9:00 a.m.	Session I: Addressing the Gaps of Current MPS Treatments/Clinical Trials (ERT, BMT, CBT) Chair: Elizabeth F. Neufeld, Ph.D. Goal: Define the hurdles investigators face in going from animal models to humans in clinical trials William S. Sly, M.D.-Addressing the Unmet Needs in MPS Treatment General discussion (20 minutes)
9:00 a.m. -10:15 a.m.	Session II: Therapeutic Strategies Directed Towards CNS and BBB Chair: Elizabeth F. Neufeld, Ph.D. Goal: Identify novel approaches and evaluate strategies, including combination therapies Speakers funded through the NIH/LSDRC PAS-04-120 (10 minutes per speaker) Elizabeth F. Neufeld, Ph.D.-Developing Aptamer-Based Therapy Patricia Dickson, M.D.-Intrathecal Enzyme Therapy for Mucopolysaccharidosis I Thomas N. Seyfried, Ph.D.-Integrated Therapeutic Approaches for Brain Ganglioside Storage Diseases Kyuson Yun, Ph.D.-MPS VII CNS Gene Therapy Using Neuronal Stem Cells Steven U. Walkley, D.V.M., Ph.D.-Substrate Reduction Therapy (SRT) and Byproduct Replacement Therapy (BRT) for Lysosomal Diseases Miguel Sena-Esteves, Ph.D.-Intraparenchymal AAV Gene Delivery in GMI-Gangliosidosis Models General discussion (15 minutes): What are the promising novel approaches in treating CNS problems in MPS? Can traditional approaches (BMT, ERT) and/or novel approaches (e.g., gene therapy, CBT, stem cells, SRT, unfolded protein response, etc.) be effective alone or in combination when treating the MPSs?
10:15 a.m. -10:30 a.m.	Break
10:30 a.m.-12:00 p.m.	Session III: Current Therapeutic Strategies Chair: Katherine Ponder, M.D. Goal: Identify the limitations and need for improvements in the traditional therapeutic approaches for MPS (15 minutes per speaker) Gordon Watson, Ph.D.-Intrathecal Gene Therapy Raquel M. Walton, V.M.D., Ph.D.-Abnormalities in Neural Progenitor Cells in a Dog Model of Lysosomal Storage Disease Adarsh Reddy, Ph.D.-Combination Gene Therapy and Bone Marrow Transplantation Frances Platt, Ph.D. -Substrate Reduction Therapy and BMT General discussion (20 minutes): What are the practical hurdles in these approaches for moving into the clinic?
12:00 p.m. -1:00 p.m.	Lunch
1:00 p.m.-3:15 p.m.	Session IV: Pre-Clinical Research Using Large Animals Chair: Mark Haskins, V.M.D., Ph.D. Goal: Determine lessons learned from the preclinical use of dogs, cats and other large animal models (15 minutes per speaker) Katherine Ponder, M.D.-Direct Systemic Gene Therapy (MPS I) Alberto Auricchio, M.D. -AAV Mediated Gene Transfer for MPS VI Jay H. Dritz, M.D.-Lentiviral-Mediated Hematopoietic-Directed Gene Therapy for Canine MPS VII John H. Wolfe, V.M.D., Ph.D.-AAV Gene Transfer in -Mannosidosis Jean-Michel Heard, Ph.D.-CNS- directed AAV (MPS I) David M. Bedwell, Ph.D.-Use of Small Molecules in Suppression of the IDUA-W402X Mutation in MPS I Christopher Eckman, Ph.D.-Enzyme Replacement for Krabbe's Disease N. Matthew Ellinwood, D.V.M., Ph.D.-Preclinical Evaluation of CNS- Directed AAV Using the MPS III B Canine Model General discussion (15 minutes): Can the positive results obtained in murine models of MPS be recapitulated in larger animal models? How can the work on these models potentially help in designing trials that will work in children?
3:15 p.m.-3:30 p.m.	Break
3:30 p.m.-4:30 p.m.	Session V: Panel Discussion Chair: Alberto Auricchio, M.D. Panelists: John H. Wolfe, V.M.D, Ph.D.; Mark Haskins, V.M.D, Ph.D.; Mark S. Sands, Ph.D.; Steven U. Walkley, D.V.M., Ph.D.; Elizabeth F. Neufeld, Ph.D.; William S. Sly, M.D.; Joanne Kurtzberg, M.D. What are the research and resource needs that will facilitate translational and clinical research addressing the CNS issues for MPS? What therapeutic strategies should be emphasized? Is gene therapy the most promising therapeutic approach to cure MPS and other LSDs? What other therapies hold the most promise for treatment and delivery of therapies to the brain? What are the limitations of these therapies?
4:30 p.m.-5:30 p.m.	Session VI: Selected Oral Poster Presentation Chair: John H. Wolfe, V.M.D., Ph.D. Andrea Ballabio-The MSD Mouse Model as a Tool to Elucidate the Pathogenetic Mechanism of MPS Agnes Chen-Study of GAG Storage in Brain by Region Following Intrathecal rhIDU Betty Chen-Developing Aptamer-Based Therapy for Lysosomal Disorders Affecting the CNS Xiucui Ma-Improvements in Mucopolysaccharidosis I Mice After Adult Retroviral Vector-Mediated Gene Therapy With Immunomodulation Stanley Tamaki -The Use of Human Central Nervous System-Stem Cells to Treat Infantile Neuronal Ceroid Lipofuscinosis
6:00 p.m.	Poster Session Reception hosted by the MPS Society
Thursday	March 8, 2007
7:30 am.-8:00 a.m.	Registration/Continental Breakfast
8:00 a.m.-10:15 a.m.	Session VII: Ongoing and Pending Clinical Trials Chair: Steven U. Walkley, D.V.M., Ph.D. Goal: Overview and lessons learned from completed clinical studies (ERT, BMT), as well as ongoing or proposed clinical trials (HSC-directed gene therapy, CNS-directed AAV-mediated gene therapy, CNS-directed neuronal stem cells). (20 minutes per speaker) Joseph Muenzer, M.D., Ph.D.-ERT Clinical Trials for MPS Mark S. Sands, Ph.D.-AAV Integration Into a miRNA Cluster is Implicated in Hepatocellular Carcinoma in Mice Ronald G. Crystal, M.D. -CNS-directed AAV Gene Therapy for Late Infantile Neuronal Ceroid Lipofuscinosis Nobuko Uchida, Ph.D.-The Use of Human Central Nervous System Stem Cells to Treat Infantile Neural Ceroid Lipofuscinosis General discussion (45 minutes): What will it take to cure MPS in children? How can the current research potentially help in designing trials that will work in children?
10:15 a.m.-10:30 a.m.	Break
10:30 a.m.-12:00 a.m.	Session VIII: Early Intervention and Meaningful Clinical Outcomes Chair: Joseph Muenzer, M.D., Ph.D. Goal: Strategize on the most effective ways for designing and implementing treatment strategies for MPS and other LSDs. (12 minutes per speaker) Charles H. Vite, D.V.M., Ph.D.-MRI of Brain Pathology and its Therapy C. Ronald Scott, M.D.-Newborn Screening for Lysosomal Storage Diseases Joanne Kurtzberg, M.D.-Treatment of MPS Syndromes with Umbilical Cord Blood Transplant Maria Louisa Escolar, M.D.-Understanding CNS Outcomes. It Is Never Too Early, but When Is It too Late To Treat? Chester B. Whitley, M.D., Ph.D.-Meaningful Clinical Outcomes General discussion (30 minutes): What are the issues and hurdles to effective therapy for MPS? e.g., newborn screening, genotype/phenotype correlations, objective end-points, combination therapies, regulatory issues, etc.
12:00 p.m.-1:00 p.m.	Lunch-Panel Discussion and Casual Working Box Lunch with MPS Parents with CNS Involved Children (A Day in the Life)
1:00 p.m.-2:30 p.m.	Session IX: Panel Discussion Chair: Giovanna Spinella, M.D. Panelists: Joseph Muenzer, M.D., Ph.D.; David A. Wenger, Ph.D., Paul M. Fernhoff, M.D.; John Hopwood, Ph.D.; Chester B. Whitley, M.D., Ph.D.; Danilo Tagle, Ph.D.; Catherine McKeon, Ph.D.; Tan Nguyen, M.D., Ph.D.; Mark S. Sands, Ph.D. What do investigators need to know to go from animal models to human trials? What will clinical trials look like? How can clinicians start to gather the functional outcomes for developing surrogate markers, standard protocol and assessment measures to apply a treatment? Which of the LSDs will most likely to be ready for gene therapy and why? Are there MPS's that will not benefit from gene therapy? Which type(s)? How will the therapy translate to other LSDs? How can the research community work to move in this direction?
2:30 p.m.-3:30 p.m.	Summary and Future Directions-Mark S. Sands, Ph.D. Report from the Panel Discussions Research priorities Research networks and collaborations Therapeutic strategies

Meeting Adjourns

Towards Clinical Progress in the Mucopolysaccharidoses
March 7 - 8, 2007
Washington Plaza Hotel
Washington, DC

Poster Presentations

Poster #1	The MSD Mouse Model as a Tool to Elucidate the Pathogenetic Mechanism of MPS	Andrea Ballabio
Poster #2	Non-Myeloablative Stem Cell Gene Delivery Effectively Establishes Long-Term Gene Expression and Mixed Chimerism in Immunocompetent Mice	Brian Bigger
Poster #3	Study of GAG Storage in Brain by Region Following Intrathecal rhIDU	Agnes Chen
Poster #4	Developing Aptamer-based Therapy for Lysosomal Disorders Affecting the CNS	Betty Chen
Poster #5	Retention of Hematopoietic cells in the Bone Niche is Regulated by Neuraminidase-1: Consequences for BM-Mediated Gene Therapy	Alessandra D'Azzo
Poster #6	Preliminary Clinical Neurologic, Cardiac, Ophthalmologic and MRI Findings in Mucopolysaccharidosis Type IIIB Dogs (MPS IIIB) Dogs	Karen Kline
Poster #7	Characterisation of Secondary Glycosphingolipid Storage in the Mucopolysaccharidoses	Emyr Lloyd-Evans
Poster #8	Improvements in Mucopolysaccharidosis I Mice after Adult Retroviral Vector-mediated Gene Therapy with Immunomodulation	Xiucui Ma
Poster #9	The Use of Human Central Nervous System-Stem Cells to Treat Infantile Neuronal Ceroid Lipofuscinosis	Stanley Tamaki
Poster #10	AAV-Mediated Gene Transfer to Muscle and Liver of MPS VI Animal Models	Alessandra Tessitore

Towards Clinical Progress in the Mucopolysaccharidoses
Washington Plaza Hotel
Washington, D.C.
March 7-8, 2007

Participant List

Organizers

Mark Haskins, V.M.D., Ph.D.
Professor of Pathology and Medical Genetics
University of Pennsylvania

Sissi Langford
Chair, Committee on Federal Legislation
National MPS Society

Catherine McKeon, Ph.D.
Senior Advisor for Genetic Research
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health

Mark S. Sands, Ph.D.
Associate Professor
Departments of Internal Medicine
Washington University in St. Louis
School of Medicine

Danilo Tagle, Ph.D.
Program Director
Neurogenetics
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Speakers

Alberto Auricchio, M.D.
Associate Professor of Medical Genetics,
Department of Pediatrics
University Federico II of Naples
Principal Investigator, Telethon Institute of Genetics and Medicine (TIGEM)

David M. Bedwell, Ph.D.
Professor
University of Alabama at Birmingham
Department of Microbiology

Ronald G. Crystal, M.D.
Professor and Chair
Department of Genetic Medicine
Weill Medical College of Cornell University

Patricia Dickson, M.D.
Assistant Professor
Harbor-University of California, Los Angeles

Jay H. Dritz, M.D.
Newborn Medicine Fellow
Washington University in St. Louis
School of Medicine

Christopher Eckman, Ph.D.
Associate Professor
Mayo Clinic

N. Matthew Ellinwood, D.V.M, Ph.D.
Assistant Professor
Companion Animal Genomics
Department of Animal Science
Iowa State University

Maria Luisa Escolar, M.D., M.S.
Director
Program for Neurodevelopmental Function in Rare Disorders
Center for Development and Learning
University of North Carolina at Chapel Hill

Paul M. Fernhoff, M.D.
Associate Professor
Human Genetics and Pediatrics
Medical Director
Emory Genetics and Emory Lysosomal Disease
Department of Human Genetics
Division of Medical Genetics
Emory University School of Medicine

Stephen C. Groft, Pharm.D.
Director
Office of Rare Diseases
National Institutes of Health

Mark Haskins, V.M.D., Ph.D.
Professor of Pathology and Medical Genetics
University of Pennsylvania

Jean-Michel Heard, Ph.D.
Head, Retrovirus and Genetic Transfer
Institute Pasteur
Paris, France

John Hopwood, Ph.D.
Professor
Women's and Children's Hospital
South Australia

Joanne Kurtzberg, M.D.
Professor of Pediatrics and Pathology
Director, Pediatric Blood and Marrow Transplant Program
Director, Carolinas Cord Blood Bank at Duke
Duke University Medical Center

Story C. Landis, Ph.D.
Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Catherine McKeon, Ph.D.
Senior Advisor for Genetic Research
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health

Joseph Muenzer, M.D., Ph.D.
Associate Professor
University of North Carolina
Department of Pediatrics

Elizabeth F. Neufeld, Ph.D.
Professor of Biological Chemistry
David Geffen School of Medicine
University of California at Los Angeles

Tan Nguyen, M.D., Ph.D.
Medical Officer
Office of Orphan Products Development
Food and Drug Administration

Fran Platt, Ph.D.
University of Oxford
Department of Pharmacology
Oxford, England

Katherine Ponder, M.D.
Associate Professor
Washington University in St. Louis
School of Medicine
Department of Internal Medicine
St. Louis, MO 63110

Adarsh S. Reddy, Ph.D.
Washington University in St. Louis

Mark S. Sands, Ph.D.
Associate Professor
Departments of Internal Medicine
Washington University in St. Louis
School of Medicine

Miguel Sena-Esteves, Ph.D.
Assistant Professor of Neurology
Massachusetts General Hospital

C. Ronald Scott, M.D.
Professor
University of Washington
Department of Pediatrics, 356320

Thomas N. Seyfried, Ph.D.
Professor
Boston College
Department of Biology

William S. Sly, M.D.
Professor and Chairman
Department of Biochemistry
Saint Louis University School of Medicine

Giovanna Spinella, M.D.
Science and Program Coordinator
Office of Rare Diseases
National Institutes of Health

Danilo Tagle, Ph.D.
Program Director
Neurogenetics
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Nobuko Uchida, Ph.D.
Vice President
Stem Cell Biology
StemCells, Inc.

Charles H. Vite, D.V.M., Ph.D.
Assistant Professor of Neurology
School of Veterinary Medicine
University of Pennsylvania

Steven U. Walkley, D.V.M., Ph.D.
Professor of Neuroscience
Albert Einstein College of Medicine

Raquel M. Walton, V.M.D, Ph.D.
Assistant Professor of Clinical Pathology
Department of Pathobiology
University of Pennsylvania School of Veterinary Medicine

Gordon Watson, Ph.D.
Scientist
Children's Hospital Oakland Research Institute

David A. Wenger, Ph.D.
Professor
Jefferson Medical College

Chester B. Whitley, M.D., Ph.D.
Professor
Department of Pediatrics, and Institute of Human Genetics
University of Minnesota

John H. Wolfe, V.M.D., Ph.D.
Professor of Pathological and Medical Genetics
Children's Hospital of Philadelphia

Kyuson Yun, Ph.D.
Associate Staff Scientist
The Jackson Laboratory

Poster Presenters

Andrea Ballabio, M.D.
Professor and Director
Telethon Institute of Genetics and Medicine (TIGEM)
Napoli, Italy

Brian Bigger, Ph.D.
Group Leader
MPS Stem Cell Research Laboratory
Giving for Living Research Centre
University of Manchester
Royal Manchester Children's Hospital
Manchester, England

Agnes Chen, M.D.
Pediatric Neurology Fellow
Harbor-University of California, Los Angeles
Medical Center
Department of Neurology

Chi-hong B. Chen, Ph.D.
Research Biochemist
University of California, Los Angeles

Alessandra D'Azzo, Ph.D.
Professor and Member
St. Jude Children's Research Hospital

Karen Kline, D.V.M., M.S.
Associate Professor
Neurology and Neurosurgery
Diplomate ACVIM Neurology
Iowa State University
College of Veterinary Medicine

Emyr Lloyd-Evans, Ph.D.
Department of Pharmacology
University of Oxford
Oxford, England

Xiucui Ma, Ph.D.
Senior Research Technician
Washington University in St. Louis
School of Medicine

Stanley Tamaki, Ph.D.
Director
Antibody and Assay Development
StemCells, Inc.

Alessandra Tessitore, Ph.D.
Postdoctoral Researcher
Telethon Institute of Genetics and Medicine (TIGEM)
Napoli, Italy

Participants

Karen Aiach
President
Alliance Sanfilippo

Amy Barkley
MPS II, Mother

Kendra Bjoraker, Ph.D.
Pediatric Neuropsychologist
University of Minnesota

Melissa Boyter
BioMarin

Jessie Brenton
MPS III A, Sister

Mati Buccini
MPS I, Aunt

Ellen Buck-McFadyen
MPS VI, Mother

Lawrence Charnas, M.D., Ph.D.
Associate Professor of Pediatrics
University of Minnesota

Steve Chesser
MPS II, Father

Joan Cohen
MPS II, Mother

Adam Cohen
MPS II

Bill Cummings
Genzyme

Olivier Danos, Ph.D.
Directeur de Recherche CNRS
Inserm U781
Bâtiment Maurice Lamy
Hôpital Necker-Enfants Malades
Paris, France

Mark Dant
The Ryan Foundation for MPS Children

Jeanne Dant
The Ryan Foundation for MPS Children

Cristin Davidson, B.S.
Sidney Weisner Laboratory of Genetic Neurological Disease
Department of Neuroscience
Rose F. Kennedy Center for Research in Mental Retardation and Human Development
Albert Einstein College of Medicine

Brian Delaney
The Ryan Foundation for MPS Children

Maggie Delaney
The Ryan Foundation for MPS Children

Denise Dengel
MPS I

Ernie Dummann
MPS III A, Father

Debbie Dummann
MPS III A, Mother

Tim Edmunds, Ph.D.
Vice President
Therapeutic Protein Research
Genzyme Corporation

Rebecca Farkas, Ph.D.
Science Policy Analyst
Office of Science Policy and Planning
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Ann Hale, Ph.D.
Executive Director
Global Organization for Lysosomal Diseases
England

Sheryl Hall
MPS III A, Mother

Gerald Hall
MPS III A, Father

Kirsten Harkins
Executive Director
The Canadian Society for Mucopolysaccharide and Related Diseases, Inc.

Paul Harmatz, M.D.
Children's Hospital Oakland

Mike Havert, Ph.D
Product Reviewer
Food and Drug Administration (FDA)

Carolyn Hinton
MPS II, Mother

Steve Holland
MPS I, Father

Amy Holland
MPS I, Mother

Jonathan Jacoby
Hide & Seek Foundation for Lysosomal Disease Research

Barbara Keeney
MPS II, Grandmother

Kris Klenke
MPS II, Mother
National MPS Society

Larry Kirch
MPS III A, Father

Karin Ludwig, M.D.
Senior Vice President
Clinical Research
Amicus Therapeutics, Inc.

Alice Martin

Claudina Bonetti Marcus
MPS I, Mother

Paige Migliozzi
MPS I, Mother

Paul J. Orchard, M.D.
Associate Professor
University of Minnesota
Department of Pediatrics

Richard L. O'Sullivan, M.D.
Senior Medical Director
Shire Human Genetic Therapies

George Sarantinos
MPS III B, Father

Athena Sarantinos
MPS III B, Mother

Les Sheaffer
MPS III, Father
Former Board Member
National MPS Society

Teri Sheaffer
MPS III, Mother
National MPS Society

Enrico Maria Surace, D.V.M.
Assistant Investigator.
Telethon Institute of Genetics and Medicine (TIGEM)
Napoli, Italy

Patty Taormino
MPS III A, Mother

Jakub Tolar, M.D., Ph.D.
Assistant Professor
University of Minnesota

Laurie Turner
Program Director
National MPS Society

William Vespe
Family Member

Barbara Wedehase, C.G.C., M.S.W.
Executive Director
National MPS Society

Ellen Welch, Ph.D.
Group Leader
PTC Therapeutic

Klane White
MPS I, Father

Kym Wigglesworth
MPS I, Mother