The ultra-rare lysosomal diseases collectively affect 1 in 3,000 individuals and are responsible for significant morbidity and disability. The Lysosomal Disease Network (LDN) has created a community of clinical investigators, patient advocacy groups (PAG), and other interested parties, to become a synergistic research and educational consortium advocating advancement of treatment for these diseases. In the past three decades, lysosomal diseases have been a test bed for some of the most innovative therapeutic modalities. In the past 4 years of NIH funding, the LDN has accelerated knowledge acquisition in the field - with 33 MyNCBI cited publications, and 12 more in press/review/preparation-and furthered the development of therapeutic options. For the next 5 years, this proposal describes 9 longitudinal studies of natural history and/or treatment, and 5 pilot studies for novel ideas under the central theme of discovery in ultra-orphan diseases. Because central nervous system (CNS) disease is the most difficult to treat and measure, there is a major emphasis on quantitative analysis of CNS structure, function and biomarkers for relevant conditions: mucopolysaccharidoses (MPS), mucolipidosis IV, Batten disease, gangliosidoses (Tay-Sachs, Sandhoff and GM1 gangliosidosis diseases), globoid cell leukodystrophy. Projects will (a) evaluate immune modulatory factors affecting treatment response in Pompe disease; (b) assess bone disease in MPS, (c) correlate renal structure and function in Fabry disease; (d) search for undiagnosed Fabry disease in high-risk populations; (e) determine outcomes of newborn screening for Krabbe disease; and (f) shorten the diagnostic odyssey. Productivity is assured by a new performance-based model, with proposals initially vetted for rigorous statistical significance, and reimbursement to investigators governed by DMCC data submission. In addition, this network: (a) supports two postdoctoral fellows each year; (b) organizes a scientific meeting WORLD Symposium published annually (February, Molecular Genetics & Metabolism); and (c) a didactic course for experts, Lysosomes 101. Global communication is provided by a list-serve with more than 3,000 subscribers, webinars, and the website LysosomalDiseaseNetwork.org.
The combined and integrated efforts of the Lysosomal Disease Network focus limited resources toward creating a network of centers with expertise in these diseases in order to solve major challenges in diagnosis, disease management, and therapy. Solutions to these problems will have direct impact on patients suffering from lysosomal diseases, with important implications for medical practice and individual quality-of-life.
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