This study is submitted to investigate the effects of calcium activated neutral protease (calpain) inhibition by the tripeptide, leupeptin, after nerve repair in a primate (Cebus apella) model. Our prior studies have consistently indicated that leupeptin, administered intramuscularly (IM) to Cebus monkeys at a dose of 18mg/kg, 2X daily for six months, following immediate or delayed median nerve transection/repair, is effective in enhancing neuromuscular recovery. There is also encouraging data which suggests that neurosensory recovery is positively affected by (IM) leupeptin treatment after immediate or delayed median nerve repair. Leupeptin has not induced adverse toxicologic effects in monkeys at this dose, route or frequency of administration. The proposed study will investigate a multiple dose range of leupeptin, orally administered, after median nerve repair in a (Cebus) monkey model. Such a study is an applied approach and will provide a dose-response for both efficacy and toxicity that is preferable for selecting the proper range of doses for human studies. The oral route of administration is also preferable for human trials since it is medically safer than the intramuscular route. The goal of our study is to determine an oral dose-response for leupeptin's efficacy and toxicity, in animals to be used as a basis for human clinical trials. Leupeptin holds significant potential as an adjunctive therapy to peripheral nerve repair in facilitating an earlier and more efficient return to motor and sensory function in humans.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Orthopedics and Musculoskeletal Study Section (ORTH)
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Badalamente, M A; Hurst, L C; Stracher, A (1992) Recovery after delayed nerve repair: influence of a pharmacologic adjunct in a primate model. J Reconstr Microsurg 8:391-7
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