The Glycoproteinoses: An International Workshop on Advances in Pathogenesis and Therapy
National Institute of Neurological Disorders and Stroke
DoubleTree Hotel and Executive Meeting Center
Rockville, Maryland, USA
April 1-2, 2004
The National Institute of Neurological Disorders and Stroke (NINDS) and the Office of Rare Diseases (ORD) at NIH along with the International Society for Mannosidosis & Related Diseases, Inc. (ISMRD) co-sponsored this workshop. This scientific workshop was organized by Dr. Danilo A. Tagle (NINDS), Dr. Allesandra d'Azzo (St. Jude's Childrens Hospital), Dr. Leena Peltonen (UCLA) and Steven Walkley (Albert Einstein). The workshop addressed the following key questions and issues:
The goals of this workshop include:
The workshop attended by approximately 50 scientists from North America, Europe and the Pacific, all with interests and experience in the study of glycoprotein storage diseases (see list of participants). Also in attendance were a number of individuals from families affected by glycoprotein storage diseases. The meeting began with a series of lectures on how proteins are glycosylated (Dr. S. Kornfeld), how they are eventually degraded in lysosomes (Dr. B. Winchester), and what happens when defects occur in lysosomes which block this normal degradation (Dr. M.Patterson). In Session 2, mechanisms by which the inherited defects in lysosomes actually cause cell dysfunction and disease were explored. Dr. D. Marks, from the laboratory of Dr. R. Pagano, and Dr. S. Walkley spoke of the importance of secondary sequestration of cholesterol and glycosphingolipids and its potential consequences in lysosomal diseases. Dr. A. Cuervo discussed the degradation of cytosolic proteins in lysosomes and of the overall mechanism of chaperone-mediated autophagy. Drs. E. Neufeld and R. Proia discussed their studies on the importance of microglia and brain inflammation as participating in lysosomal disease pathogenesis, as well as possible significant differences between different types of disorders in terms of the microglial-mediated response. Dr. A. d'Azzo spoke of mechanisms contributing to neuron death in the lysosomal disease, GM1 gangliosidosis. Sessions 3 and 4 were focused on discussions of many available animal models of glycoprotein storage diseases as well as molecular mechanisms contributing to individual diseases. Included here were reports of glycoprotein storage diseases in mice, guinea pigs, cats, dogs, goats and cattle, and presentations by Drs. M. Haskins, A. Jalanko, J. Hopwood, D. Schindler, A. d'Azzo, P. Lobel, and W. Sly. There were also 2 sessions of speakers focused on therapeutic strategies in lysosomal diseases. Included here were reports on enzyme replacement therapy in alpha-mannosidosis by Dr. P. Saftig, mechanisms by which microglia may transfer enzyme to diseased neurons by Dr. K. Dobrenis, the use of cord blood and hematopoietic stem cell transplants by Drs. M. Escolar and C. Peters, respectively, and the use of adenoviral and lentiviral vectors for gene therapy by Drs. M. Sands and J. Medin, respectively. This session ended with a report on the use of an adenoviral vector for the treatment of brain disease in an animal model of alpha-mannosidosis by Dr. C. Vite.
Several new investigators to the field were also invited to attend the meeting and to present their findings on lysosomal diseases, including Dr. Y-P Wu (mechanisms of inflammation in storage diseases), Dr. C. Tifft (surrogate markers of lysosomal disease progression), Dr. K. Ohmi (the role of gliosis in storage disease), Dr. M. Ellinwood (a newly discovered model of mucopolysaccharidosis type IIIB), Dr. M. Yoshimitsu (the use of lentiviral vectors in gene therapy), Dr. G. Yogalingam (the use of PPCA as therapy for sialidosis) and Dr. D. Wang (enzyme replacement therapy in sialidosis and galactosialidosis).
Recommendations
The meeting closed with a roundtable discussion of pathogenic mechanisms, animal models, treatment strategies, future research priorities and research collaborations, and funding strategies, chaired by Dr. S. Kornfeld and addressed by Drs. M. Haskins, J. Hopwood, L. Neufeld, D Malm, and W. Sly. Consensus emerged on several points. Firstly, one of the major areas where our knowledge of glycoprotein storage diseases was believed most limited was in the actual mechanisms by which lysosomal dysfunction leads to cell and organ failure, particularly for brain as well as for bone and cartilage. Secondly, the availability of animal models of lysosomal diseases was viewed as a major research resource for both understanding issues of pathogenesis and for evaluating potential therapies. The one notable omission in terms of disease models was of a mouse model of fucosidosis, which many felt would be a major resource that should be developed as soon as possible. Finally, all agreed that the meeting had successfully brought together key leaders in the field and that many new collaborations had been established, and that additional substantial progress in understanding and in treating the glycoproteinoses could be anticipated.
The Glycoproteinoses: An International Workshop on Advances in Pathogenesis and Therapy
April 1-2, 2004
DoubleTree Hotel and Executive Meeting Center
Rockville, MD
Chairs -- Alessandrad'Azzo (Memphis), Leena Peltonen (Helsinki) and Steven Walkley (NewYork)
Day 1 | |
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7:30-8:00 | Continental Breakfast available |
8:00-8:15 | Welcome and Introduction of representatives from NINDS and ORD: Meeting Chairs Welcome from NINDS (Dr. Audrey Penn) and ORD (Dr. Steven Groft) Statement of workshop goals: Meeting Chairs |
8:15-10:00 | Session 1 -- Glycoprotein Structure and Function and Disorders of Glycoprotein Metabolism (Chair:Harry Schacter, University of Toronto) ]
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10:00-10:30 | Coffee Break (with poster viewing) |
10:30-12:30 | Session 2 -- Mechanisms of Disease with Relevance to the Glycoproteinoses (Chair: John Hopwood, Women's and Children's Hospital, Adelaide)
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12:30-2:00 | LUNCH |
2:00-3:30 | Session 3 -- Animal Models and Pathogenic Cascades I (Chair: Alessandra d'Azzo, St. Jude's Children's Hospital)
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3:30-4:00 | Coffee Break (with poster viewing) |
4:00-5:30 | Session 4 -- Animal Models and Pathogenic Cascades II (Chair: Steven Walkley, AlbertEinstein College of Medicine)
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6:00-7:00 | Poster Discussion (Chairs: Mark Haskin and Richard Proia)
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7:00 | Evening Session -- Reception hosted by the International Society for Mannosidosis and Related Disorders (ISMRD)
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Day 2 | |
8:00-8:30 | Continental Breakfast available |
8:30-10:00 | Session 5 -- Therapeutic Strategies I (Chair :Elizabeth Neufeld, UCLA)
Enzyme Replacement Therapy
Hematopoietic Cell Therapy
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10:00-10:30 | Coffee Break (with poster viewing) |
10:30-12:00 | Session 6 -- Therapeutic Strategies II (Chair: Bryan Winchester, University College, London)]
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12:00-1:00 | LUNCH |
1:00-3:00 | Session 7 -- Summary and Future Directions (Chair: Stuart Kornfeld, Washington University) (Discussants: Mark Haskins, John Hopwood, Dag Malm, Elizabeth Neufeld, Harry Schacter, William Sly, and Danilo Tagle)
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3:00 | Meeting close |
Workshop Organizers
Dr. Alessandra d'Azzo
Department of Genetics
St. Jude Children's Research Hospital
Dr. Leena Peltonen
UCLA Department of Human Genetics
University of California Los Angeles
Dr. Danilo A. Tagle
Neurogenetics
NINDS, NIH
Dr. Steven U. Walkley
Department of Neuroscience
Rose F. Kennedy Center for Research in Mental Retardation and Human Development
Albert Einstein College of Medicine
Invited Speakers/Session Leaders/Discussants:
Dr. Ana Marie Cuervo
Department of Anatomy andStructural Biology
Albert Einstein College of Medicine
Dr. Kostantin Dobrenis
Department of Neuroscience
Albert Einstein College of Medicine
Dr. Mark Haskins
Department of Pathobiology
Center for Comparative Medical Genetics
School of Veterinary Medicine
Dr. John Hopwood
Dept. of Chemical Pathology
Women's and Children's Hospital
Dr. Emil Kakkis
Bio Marin Pharmaceutical Inc.
Dr. Stuart Kornfeld
Div. of Hematology-Oncology
Dept. of Medicine
Washington University School of Medicine
Dr. Joanne Kurtzberg
Pediatric and Adult Bone Marrow Transplant Programs
Duke University Medical Center
Dr. Peter Lobel
Department of Pharmacology
Robert Wood Johnson Medical School
Center for Advanced Biotechnology and Medicine
Dr. Dag Malm
University Hospital of Northern Norway
Dr. David Marks
Department of Biochemistry and Molecular Biology
Mayo Clinic and Foundation
Dr. J. Medin
Division of Experimental Therapeutics
Ontario Cancer Institute, Toronto, Canada.
Dr. Elizabeth Neufeld
Dept. of Biological Chemistry
UCLA School of Medicine
Dr. Marc Patterson
Division of Pediatric Neurology
Columbia University
Dr. Charles Peters
Inherited Metabolic Storage Disease Program
University of Minnesota
Dr. D. Prockop
Center for Gene Therapy
Tulane University Health Sciences Center
Dr. Richard Proia
Genetics of Development and Disease
National Institutes of Health
Dr. Paul Saftig
Biochemisches Institut
Christian-Albrechts-Universität Kiel
Dr. Mark Sands
Department of Internal Medicine
Washington University School of Medicine
Dr. Harry Schachter
Department of Structural Biology and Biochemistry
The Research Institute
The Hospital for Sick Children
Dr. Detlev Schindler
Director, Cell Culture, Biochemistry and Flow Cytometry Division
Department of Human Genetics
University of Wuerzburg
Dr. William Sly
Dept. of Biochemistry and Molecular Biology
St. Louis University
Dr. Ole Kristian Tolersrud
Department of Medical Biochemistry
Institute of Medical Biology
University of Tromso
Dr. Bryan Winchester
Biochemistry, Endocrinology and Metabolism Unit
Institute of Child Health
Last updated February 09, 2005