Family Conference
Personal Reflections

Scientific Conference
Children and Youth Program

The Third International Workshop on Glycoproteinoses was held July 28 and 29, 2012 at the Crowne Plaza Hotel in N. Charleston, South Carolina. Concurrent scientific and family sessions were held during this two day meeting co-hosted by the Greenwood Genetic Center and ISMRD, the International Advocate for Glycoprotein Storage Diseases. The primary goal of the scientific meeting was to bring together rare disease experts from various disciplines. This was accomplished, and the conference achieved an unprecedented level of scientific expertise focused on the glycoproteinoses. Dr. Richard Steet (Biochemistry and Molecular Biology, University of Georgia Complex Carbohydrate Research Center) set the bar for excellence, launching the conference with his presentation “Overview of glycoproteinoses, old and new questions – looking to contemporary research for answers”. Dr. Steet described the complex cellular and molecular pathogenesis of the glycoprotein disorders, challenging us to broaden our view of these diseases. We need to focus not only on intracellular lysosomal storage but also on critical secondary effects in the extracellular matrix arising from inflammatory cascades, oxidative stress, altered calcium homeostasis, and autophagy. Dr. Emil Kakkis (EveryLife Foundation for Rare Diseases) gave an eye-opening presentation about regulatory processes and the hurdles that must be overcome for rare disease therapies to reach the marketplace. Mark Haskins (Center for Comparative Medical Genetics, University of Pennsylvania School of Veterinary Medicine) presented the latest developments from his area of expertise, therapy for human genetic diseases in large animal models. These first three talks built the framework for many discussions, all with the ultimate goal of answering this question: How can we treat these diseases?

Pathogenesis of the glycoproteinoses and the implications for therapeutic interventions were further explored by eminent scientists. Stuart Kornfeld (Washington University School of Medicine) explored mannose 6-phosphate dependent trafficking from the molecular level of the critical phosphotransferase enzyme. Roberto Zoncu (Postdoctoral Fellow in the laboratory of David Sabatini, Whitehead Institute for Biomedical Research) discussed the lysosome as a key organelle for metabolism and presented his research of the mTOR complex 1 protein kinase, a master growth regulator activated by amino acid signals from within the lysosomal lumen. Peter Lobel (Center for Advanced Biotechnology and Medicine, Rutgers University) discussed lysosomal proteomics, explaining both the “disease to protein” and “protein to disease” approaches for disease discovery and development of protein-based therapeutics. William Sly (Endowed Chair in Biochemistry and Molecular Biology Saint Louis University) presented the topic of targeted therapeutic proteins. He discussed glutathione receptor targeted liposomes to deliver drug to the brain and maintain the neuroprotective function of the blood-brain-barrier. David Bedwell (University of Alabama at Birmingham) presented nonsense suppression therapy.

Jon Davids (Shriners Hospital for Sick Children, Sacramento) talked about the skeletal manifestations of the glycoproteinoses and set the stage for two talks exploring the bone disease of mucolipidosis II and III. From the patient bedside perspective, Jules Leroy (Former Professor and Chairman of Pediatrics Ghent University, Belgium) covered prenatal, early and late skeletal features of ML. From the laboratory bench perspective, Dr. Steet discussed the role of excess cathepsin K in cartilage defects in a zebrafish model of ML II.

Troy Lund (Pediatric Hematology, Oncology and BMT, University of Minnesota) presented a comprehensive overview of hematopoietic cell transplant in the glycoproteinoses. Rosanne Taylor and Jessica Fletcher presented the pathophysiology of fucosidosis and enzyme infusion therapy in canine fucosidosis. Dr. Taylor’s work on fucosidosis dogs led to the first bone marrow transplant for human fucosidosis. Alessandra d’Azzo, (St. Jude’s Children’s Research Hospital) presented the status of gene therapy for galactosialidosis and the post-doctoral fellow from her lab, Shai White-Gilbertson, discussed the role of neuraminidase 1 in lysosomal exocytosis and disease pathogenesis. Line Borgwardt (Copenhagen University Hospital, Denmark) presented the early results of European trials of enzyme replacement for alpha-mannosidosis. Miao He and Ali Pervaiz from Emory University discussed high resolution urinary oligosaccharide analysis by MALDI-TOF mass spectrometry and the use of this testing in the diagnosis of aspartylglucosaminuria in one of their patients. Tim Wood (Biochemical Genetics Laboratory at Greenwood Genetic Center) explored the very rare disorder known as Schindler disease and the unique properties of alpha-N-acetylgalactosaminidase (NAGA enzyme).

All presenters and attendees benefited from the thoughtful discussions and questions inspired by the conference. Prior to closure of the conference, the timing of the next International Workshop on Glycoproteinoses was discussed with the entire group. The expectation is that a similar meeting will be useful and necessary within three years.

Third International Workshop on Glycoproteinoses Speaker List

• David Bedwell, Ph.D. – University of Alabama at Birmingham, Birmingham, Alabama
• Line Borgwardt, M.D. – Copenhagen University Hospital, Denmark
• Nila Coley – Cedartown, Georgia
• Alessandra d’Azzo, Ph.D. – St. Jude Children’s Research Hospital, Memphis, Tennessee
• Ron R. Davids, M.D. – Shriners Hospitals for Sick Children, Sacramento, California
• Jessica Fletcher – The University of Sydney, Australia
• Mark Haskin, V.M.D., Ph.D. – University of Pennsylvania, Philadelphia, Pennsylvania
• Miao He, Ph.D. – Emory University School of Medicine, Decatur, Georgia
• Lucia Horowitz, Ph.D. – Greenwood Genetic Center, Greenwood, South Carolina
• Emil Kakkis, M.D., Ph.D. – Every Life Foundation for Rare Diseases, Novato, California
• Stuart Kornfeld, M.D. – Washington University School of Medicine, St. Louis, Missouri
• Dawn Jacob Laney, MS, CCRC – Emory University School of Medicine, Decatur, Georgia
• Jules Leroy, M.D., Ph.D. – Greenwood Genetic Center, Visiting Senior Scholar from Belgium
• Peter Lobel, Ph.D. – Rutgers University, Piscataway, New Jersey
• Troy Lund, Ph.D., M.D. – University of Minnesota, Minneapolis, Minnesota
• Marc C. Patterson, M.D. – Mayo Clinic, Rochester, Minnesota
  Muhammad Pervaiz, M.D. – Emory University School of Medicine, Decatur, Georgia
• Joseph B. Ryan, Ph.D. – Clemson University, Clemson, South Carolina
• Carlos F. Salinas, D.M.D. – Medical University of South Carolina, Charleston, South Carolina
• Ida Vanessa Doederlein Schwartz, M.D. Ph.D. – Federal University of Rio Grande do Sul, Brazil
• William Sly, M.D. – Saint Louis University School of Medicine, St. Louis, Missouri
• Richard Steet, M.D. – University of Georgia, Athens, Georgia
• David M. Steinhorn M.D. – Ann and Robert H. Lurie Children’s Hospital, Chicago, Illinois
• Ronald Teed, M.D. – Children’s Eye Specialists, Charleston, South Carolina
• Rosanne Taylor, Ph.D. – The University of Sydney, Australia
• Melinda Whetsell, MS, RD, LD – Greenwood Genetic Center, N. Charleston, South Carolina
• Shai White-Gilbertson, Ph.D. – St. Jude’s Children’s Research Hospital, Memphis, Tennessee
• Tim Wood, Ph.D. – Greenwood Genetic Center, Greenwood, South Carolina
• Roberto Zoncu, Ph.D. – Whitehead Institute, Cambridge, Massachusetts