LEUPEPTIN IN RECOVERY AFTER NERVE REPAIR

神经修复后亮肽素的恢复

• 批准号: 3404628
• 负责人: LAWRENCE C HURST
• 金额: $ 23.28万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404628
• 关键词: Ceboidea; calcification stimulant; calpain; disease /disorder model; dosage; drug administration routes; drug adverse effect; histology; nervous system regeneration; neuromuscular function; neuropharmacology; nonhuman therapy evaluation; oligopeptides; peripheral nervous system disorders; protease inhibitor

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.

本研究旨在探讨钙激活剂 中性蛋白酶（钙蛋白酶）抑制三肽，亮抑酶肽， 灵长类动物（Cebus apella）模型中的神经修复。 我们之前的研究 一致表明，亮抑酶肽，肌肉注射（IM）， 以18 mg/kg的剂量，每天2次，持续6个月， 立即或延迟正中神经切断/修复， 促进神经肌肉恢复。 还有一些令人鼓舞的数据， 表明神经感觉恢复受到（IM）的积极影响 立即或延迟正中神经修复后的亮抑酶肽治疗。 亮抑酶肽在此浓度下未在猴中诱导不良毒理学作用。 剂量、给药途径或频率。 所提出的研究将调查亮抑酶肽的多剂量范围， 在（Cebus）猴模型中正中神经修复后口服给药。 这样的研究是一种应用方法，将提供剂量反应， 同时考虑疗效和毒性， 用于人体研究的剂量范围。 口服给药途径也是 更适合人体试验，因为它在医学上比 肌肉注射。 我们研究的目的是确定亮抑酶肽的口服剂量反应， 疗效和毒性，在动物中用作人类临床的基础 审判 亮抑酶肽具有显著的潜力，作为一种预防性治疗， 周围神经修复促进更早，更有效地 恢复人类的运动和感觉功能。

项目成果

Recovery after delayed nerve repair: influence of a pharmacologic adjunct in a primate model.

延迟神经修复后的恢复：灵长类动物模型中药理学辅助剂的影响。

• DOI: 10.1055/s-2007-1006724
• 发表时间: 1992
• 期刊: Journal of reconstructive microsurgery
• 影响因子: 2.1
• 作者: Badalamente,MA;Hurst,LC;Stracher,A
• 通讯作者: Stracher,A

The venoarteriolar reflex in diabetic and other neuropathies.

糖尿病和其他神经病中的静脉小动脉反射。

• DOI: 10.1212/wnl.39.11.1490
• 发表时间: 1989
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Moy,S;Opfer-Gehrking,TL;Proper,CJ;Low,PA
• 通讯作者: Low,PA

Enhancement of neuromuscular recovery after nerve repair in primates.

增强灵长类动物神经修复后的神经肌肉恢复。

• DOI: 10.1016/0266-7681_87_90015-5
• 发表时间: 1987
• 期刊: Journal of hand surgery (Edinburgh, Scotland)
• 作者: Badalamente,MA;Hurst,LC;Paul,SB;Stracher,A
• 通讯作者: Stracher,A

Localization and inhibition of calcium-activated neutral protease (CANP) in primate skeletal muscle and peripheral nerve.

灵长类骨骼肌和周围神经中钙激活中性蛋白酶（CANP）的定位和抑制。

• DOI: 10.1016/0014-4886(87)90248-2
• 发表时间: 1987
• 期刊: Experimental neurology
• 影响因子: 5.3
• 作者: Badalamente,MA;Hurst,LC;Stracher,A
• 通讯作者: Stracher,A

Neuromuscular recovery using calcium protease inhibition after median nerve repair in primates.

灵长类动物正中神经修复后使用钙蛋白酶抑制进行神经肌肉恢复。

• DOI: 10.1073/pnas.86.15.5983
• 发表时间: 1989
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Badalamente,MA;Hurst,LC;Stracher,A
• 通讯作者: Stracher,A