Oral administration of a nonimmunosuppressant FKBP-12 ligand speeds nerve regeneration.
We recently showed that s.c. injections of a nonimmunosuppressant FK506 binding protein-12 (FKBP-12) ligand (V-10,367) accelerates nerve regeneration in the rat sciatic nerve crush model. Here we examined the oral efficacy of this compound for speeding nerve regeneration. Rats receiving V-10,367 (5, 15 or 50 mg/kg/day) by oral gavage all demonstrated an increase in nerve regeneration compared to vehicle-treated controls. Functional recovery was observed earliest and axonal calibers of regenerating axons in the soleus nerve were largest in the 15 mg/kg group, mean axonal areas being increased by 66% compared to controls. Orally active nonimmunosuppressant FKBP-12 ligands may be useful for the treatment of human peripheral nerve disorders.
Gold
B G
BG
Center for Research on Occupational and Environmental Toxicology/L606 and Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Zeleny-Pooley
M
M
Chaturvedi
P
P
Wang
M S
MS
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008024:Ligands; D008297:Male; D008854:Microscopy, Electron; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D008024:Ligands; D022021:Tacrolimus Binding Proteins