LEUPEPTIN IN RECOVERY AFTER NERVE REPAIR

这项研究是为了研究钙激活的影响。 中性蛋白酶(钙蛋白酶)被三肽亮肽素抑制后 灵长类(Cebus Apella)模型的神经修复。我们之前的研究已经 一直表明，肌肉注射亮肽素(IM)对 CEBUS猴18 mg/kg，每日2次，连续6个月 立即或延迟正中神经切断/修复，在 促进神经肌肉的恢复。也有令人鼓舞的数据显示 提示(IM)对神经感觉恢复有积极影响 正中神经修复后立即或延迟应用亮肽素治疗。 亮肽素目前还没有对猴子产生不良毒理作用。 给药的剂量、途径或频率。 这项拟议的研究将研究亮肽素的多剂量范围， 口服，在正中神经修复(CEBUS)猴模型。 这种研究是一种实用的方法，将为 既有疗效又有毒性，更适合选择合适的 人体研究的剂量范围。口服给药途径也是 更适合于人体试验，因为它在医学上比 肌肉内路径。 我们研究的目标是确定亮肽素的口服剂量反应。 在动物身上的疗效和毒性，将作为人类临床的基础 审判。亮肽素作为一种辅助疗法具有巨大的潜力 周围神经修复在促进早期和更有效的 恢复人类的运动和感觉功能。

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.