Reviving the use of inhibitors of matrix metalloproteases in spinal cord injury: a case for specificity.

Abstract

At present, there are no restorative therapies in the clinic for spinal cord injury, with current treatments offering only palliative treatment options. The role of matrix metalloproteases is well established in spinal cord injury, however, translation into the clinical space was plagued by early designs of matrix metalloprotease inhibitors that lacked specificity and fears of musculoskeletal syndrome prevented their further development. Newer, much more specific matrix metalloprotease inhibitors have revived the possibility of using these inhibitors in the clinic since they are much more specific to their target matrix metalloproteases. Here, the evidence for use of matrix metalloproteases after spinal cord injury is reviewed and researchers are urged to overcome their old fears regarding matrix metalloprotease inhibition and possible side effects for the field to progress. Recently published work by us shows that inhibition of specific matrix metalloproteases after spinal cord injury holds promise since four key consequences of spinal cord injury could be alleviated by specific, next-generation matrix metalloprotease inhibitors. For example, specific inhibition of matrix metalloprotease-9 and matrix metalloprotease-12 within 24 hours after injury and for 3 days, alleviates spinal cord injury-induced edema, blood-spinal cord barrier breakdown, neuropathic pain and restores sensory and locomotor function. Attempts are now underway to translate this therapy into the clinic.