NEUROMUSCULAR RECOVERY AFTER PERIPHERAL-NERVE REPAIR - EFFECTS OF AN ORALLY-ADMINISTERED PEPTIDE IN A PRIMATE MODEL

Oral delivery of the tripeptide calpain inhibitor, leupeptin, after me dian nerve transection and epineural nerve repair in primates (Cebus a pella) was studied for its potential benefits to neuromuscular recover y. Results of a controlled, dose-response study indicated that leupept in was absorbed into plasma by the oral route of administration. When plasma leupeptin concentrations were 3 mu g/ml or greater, morphologic and functional motor recovery were facilitated after nerve repair. Se rial testing in hematology, clotting, and serum biochemistry showed th at there were no adverse effects, when leupeptin was administered twic e daily for 6 months following nerve repair. These data indicate that leupeptin is an effective and safe pharmaceutic adjunct to nerve repai r and may have clinical benefits in humans, where the oral route is a much preferred method of delivery.