Although individually rare """"""""orphan"""""""" conditions, the lysosomal diseases collectively affect 1 in 6,000 individuals and are responsible for a significant disability and disease burden. These diseases have become a test bed for some of the most innovative and advanced experimental treatments. The rarity of each lysosomal disease means that no single medical research center has an opportunity to see the entire spectrum, or to acquire sufficient numbers to adequately test new therapies. Thus, collaborative clinical research on these rare disorders and their treatment is absolutely crucial to make substantial progress. The Lysosomal Disease Network brings together more than 500 researchers and clinicians across the country, Patient Advocacy Groups (PAG), and other interested partners, and has generated a synergistic research and educational consortium to advance treatment of these diseases. In this proposal, longitudinal studies of the natural history of 11 lysosomal disease categories and 7 pilot studies of measurement of outcome and phase l/ll clinical trials are focused on several themes. Central nervous system (CNS) disease has been the most difficult to treat as well as to measure. A significant focus will be on quantitative methods of CNS structure and function providing a standard toolbox across the network in the Mucopolysaccharidoses (MPS), Batten disease, Niemann-Pick type C, Mucolipidosis type IV, Late Infantile Neuronal Ceroid Lipofuscinosis, Glycoproteinoses, GM2-gangliosidoses, and Wolman disease. A study on Pompe disease focuses primarily on the immune modulatory factors affecting treatment response. Additionally, we include a study on bone disease in the MPS and a set of innovative studies on Fabry disease in which collaborators will carry out the natural history of kidney structure and function, pulmonary function as a marker of disease progression in children, and identification of Fabry disease among high-risk populations. We will provide support for all of these projects, leveraging additional resources from PAG and industry, in the hope of fostering research on other lysosomal diseases and providing the impetus for more in-depth studies of pathophysiology and treatment. In addition, this network will provide substantial support for at least two postdoctoral trainees each year for career development in lysosomal diseases as well as a national meeting (WORLD Symposium) for sharing of research findings, education, and network synergy. A web-site www.LysosomalDiseaseNetwork.org already provides an educational, research, and clinical resource for the Network, patients, physicians, and the public.
The combined and integrated efforts of the Lysosomal Disease Network will focus limited resources toward creating a network of centers with expertise in one or more of 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, and important implications for medical practice.
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