Dr. Stracher studies the role of proteases in muscle wasting diseases and the use of low molecular weight protease inhibitors as potential therapeutic agents in treating these disorders. He has been studying molecular mechanisms responsible for neuromuscular degeneration and the role of thiol proteases such as calpain and its inhibitors in this process. Dr. Stracher has recently tested this hypothesis in the mdx mouse, a model for the human form of Duchenne muscular dystrophy and has found that intramuscular administration of the calpain inhibitor leupeptin inhibited muscle degeneration as assessed by histologic analysis and muscle strength testing (see reference 3). These studies followed the more extensive studies in primates after median nerve transaction in the mid-forearm. Both intramuscular and oral administration of the calpain inhibitor leupeptin led to almost total neuromuscular recovery after 3 months treatment as judged by histochemical analysis. These and other results have given rise to the formulation of a more common cytotoxic pathway known as the Ca++/calpain hypothesis which may be responsible for a number of related neuromuscular and neurodegenerative disorders (see reference 5).
Funded by the National Institutes of Health - NINDS.
1. Stracher, A., Calpain Inhibitors as Neuroprotective Agents in Neurodegenerative Disorders. Int'l Tinnitus Journal, Vol. 3, No. 2, 1-5 (1998).
2. Wang, J., Ding, D., Shulman, A., Stracher, A. And Salvi, R.J., Leupeptin Protects sensory hair cells from acoustic trauma, NeuroReport 10, 811-816 (1999).
3. Badalamente, M.A. and Stracher, A., Delay of degeneration and necrosis in mdx mice by calpain inhibition, Muscle and Nerve 23, 106 (2000).
4. Cheng, A.,J., Huang, T., Stracher, A., Kim, A., Liu, W., Malgrange, B., LeFebrre, P., Shulman, A., and Van DeWater, T., Calpain Inhibitors protect auditory sensory cells from Hypoxia and Neurotrophin-withdrawal induced Apoptosis, Brain Research 850, 234-243 (1999).
5. Stracher, A., Calpain inhibitors as therapeutic agents in nerve and muscle degeneration, in, Ototoxicity, ed. Henderson, Salvi, Ann. N.Y. Acad. Sci., 884, 52-56, 1999.