Neuromuscular Recovery After Peripheral Nerve Repair: Effects of an Orally-Administered Peptide in a Primate Model

ABSTRACT

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