1994 Muscular Dystrophy Association (MDA) Research Grant Awards -- CMT only 1) Detroit - Wayne State University John Kamholz, M.D., Ph.D. (Originally at Univ of Pennsylvania) Molecular pathogenesis of demyelination in Charcot-Marie-Tooth disease Research Grant: $40,500 07/01/94 - 06/30/95 (YEAR 01) Summary: Defects in the peripheral myelin protein, PMP22, have been implicated in causing myelin breakdown in the peripheral nervous system resulting in CMT. Researchers will study the role of PMP22 in Schwann cells, the myelin-forming cell of the peripheral nervous system. By constructing transgenic mouse strains expressing either mutant forms or overexpressing PMP22 the cause of myelin breakdown may be determined. 2) Detroit - Wayne State University Michael E. Shy, M.D. Remyelinating peripheral nerves in Trembler J mice with genetically labeled mouse Schwann cells Research Grant: $52,500 07/01/94 - 06/30/95 (YEAR 02), $55,125 07/01/95 - 06/30/96 (YEAR 03) Summary: A project to develop a treatment of Charcot-Marie-Tooth (CMT) disease in which normal Schwann cells are transplanted into nerves to replace the damaged Schwann cells in the Trembler J mouse model of Charcot-Marie-Tooth disease. 3) Durham - Duke University Kamel Ben Othmane, M.D. Genetic and physical mapping studies in autosomal recessive Charcot-Marie-Tooth disease (CMT4) Research Fellowship: $28,000 01/01/95 - 12/31/95 (YEAR 02) Advisor: Jeffery Vance, M.D., Ph.D. Summary: A project to investigate the genetic variation observed in Charcot-Marie- Tooth type 4, and to find the identity of the CMT4A gene defect. 4) Philadelphia - Children's Hospital of Philadelphia Phillip F. Chance, M.D. Genetic analysis of Charcot-Marie-Tooth neuropathy Genetics Research Grant: $56,771 09/01/94 - 08/31/95 (YEAR 03) Summary: Studies to isolate the gene or genes that, when defective, result in one type of Charcot-Marie-Tooth disease. 5) Philadelphia - Children's Hospital of Philadelphia Hidenori Kiyosawa, Ph.D. Molecular analysis of the Charcot-Marie-Tooth 1A/HNPP region on chromosome 17 Research Fellowship: $25,000 07/01/94 - 06/30/95 (YEAR 01), $28,000 07/01/95 - 06/30/96 (YEAR 02) Advisor: Phillip Chance, M.D. Summary: Two human conditions which cause inherited disorders of the peripheral nerves, Charcot-Marie-Tooth disease, will be studied with molecular biology methods in order to understand how the diseases arise. 6) Philadelphia - Children's Hospital of Philadelphia Mena Scavina, D.O. Genetic studies in three peripheral neuropathic disorders Research Fellowship: $25,000 07/01/94 - 06/30/95 (YEAR 01), $28,000 07/01/95 - 06/30/96 (YEAR 02) Advisor: Phillip Chance, M.D. Summary: Genetic techniques will be used to isolate and study the gene which may be responsible for the following three neuromuscular disorders: Charcot-Marie-Tooth neuropathy type 1C, hereditary motor systems disease, and familial brachial plexus neuropathy. 7) Philadelphia - Children's Hospital of Philadelphia Kenneth H. Fischbeck, M.D. Connexin and X-linked Charcot-Marie-Tooth disease Genetics Research Grant: $78,840 01/01/94 - 12/31/94 (YEAR 01), $82,782 01/01/95 - 12/31/95 (YEAR 02), $86,922 01/01/96 - 12/31/96 (YEAR 03) Summary: This project will study how defects in a newly discovered Charcot-Marie- Tooth disease gene cause destruction of peripheral nerve. 8) Dallas - University of Texas Southwestern Medical Center Scott T. Brady, Ph.D. Axon glia interactions in Trembler mouse and Charcot-Marie-Tooth disease Research Grant: $52,500 01/01/95 - 12/31/95 (YEAR 02), $55,125 01/01/96 - 12/31/96 (YEAR 03) Summary: The mechanisms of neuron wasting and degeneration in Charcot-Marie-Tooth disease will be examined in order to identify treatments or enhance function in those individuals with the disease and related diseases. 9) Houston - Baylor College of Medicine Nacer E. Abbas, Ph.D. Molecular characterization of the Charcot-Marie-Tooth disease type 1A duplication Research Fellowship: $12,500 01/01/94 - 06/30/94 (YEAR 01) Advisor: James Lupski, M.D., Ph.D. Summary: A project to determine the exact molecular structure of the most common genetic cause of Charcot-Marie-Tooth disease: The CMT1A duplication. 10) Houston - Baylor College of Medicine Sanjay I. Bidichandani, Ph.D. Charcot-Marie-Tooth disease type 1A: Development of a transgenic mouse model and investigation of a gene therapeutic strategy Research Fellowship: $25,000 01/01/95 - 12/31/95 (YEAR 01), $28,000 01/01/96 - 12/31/96 (YEAR 02), $28,000 01/01/97 - 12/31/97 (YEAR 03) Advisor: Pragna Patel, Ph.D. Summary: A mouse model for the most common subtype of Charcot-Marie-Tooth disease (type 1A) will be developed. A specific gene therapy strategy will be investigated as a possible treatment. 11) Houston - Baylor College of Medicine James R. Lupski, M.D., Ph.D. Molecular genetics of Charcot-Marie-Tooth disease Genetics Research Grant: $77,112 11/01/94 - 10/31/95 (YEAR 02), $80,968 11/01/95 - 10/31/96 (YEAR 03) Summary: Defects will be identified in the genes responsible for inherited diseases of the peripheral nerves. This will lead to a better understanding of the disease process, as well as, the development of DNA-based diagnostic tests, and rational approaches to therapy. 12) Houston - Baylor College of Medicine Tatsufumi Murakami, M.D., Ph.D. Recombination within CMT1A-REP leading to inherited neuropathies Research Fellowship: $25,000 01/01/95 - 12/31/95 (YEAR 01), $28,000 01/01/96 - 12/31/96 (YEAR 02) Advisor: James Lupski, M.D., Ph.D. Summary: This project is aimed at determining the molecular structures and recombination mechanisms leading to Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP). 13) New South Wales - University of Sydney Garth A. Nicholson, M.D., Ph.D. Mapping the mutation for hereditary sensory neuropathy Genetics Research Grant: $39,780 01/01/95 - 12/31/95 (YEAR 01), $39,780 01/01/96 - 12/31/96 (YEAR 02), $39,780 01/01/97 - 12/31/97 (YEAR 03) Summary: This study aims to find the gene mutation causing a form of hereditary sensory neuropathy which results in sensory loss and muscle wasting in the hands and feet, and appears related to Charcot-Marie-Tooth disease.