Composition and methods for the treatment of peripheral nerve injury

Abstract

Provided herein are methods of treating a peripheral nerve injury in a subject. The methods include administering to the subject at or near the site of the peripheral nerve injury an effective amount of a composition comprising an agent that promotes remyelination of the peripheral nerve. Also provided are methods of determining whether a peripheral nerve injury has a capacity for recovery. The methods include selecting a subject with a peripheral nerve injury, administering to the subject a first dose of a composition comprising and agent that promote remyelination and detecting after the first dose one or more characteristics of peripheral nerve recovery, the presence of one or more characteristics of peripheral nerve recovery indicating a peripheral nerve injury has a capacity for recovery and the absence of characteristics of peripheral nerve recovery indicating a peripheral nerve injury without a capacity for recovery.

1 .- 12 . (canceled) 
     
     
         13 . A method for determining whether an injured peripheral nerve has capacity for recovery comprising:
 (a) administering to a subject with an injured peripheral nerve a test composition comprising an agent that promotes transient peripheral nerve activity in injured peripheral nerves having a capacity for recovery; and   (b) detecting in the presence of the test composition one or more characteristics of transient peripheral nerve activity in the injured peripheral nerve, wherein the presence of transient peripheral nerve activity indicates the injured peripheral nerve has capacity for recovery.   
     
     
         14 . The method of  claim 13 , wherein the agent that promotes transient peripheral nerve activity in injured peripheral nerves having a capacity for recovery is 4-Aminopyridine (4-AP) or a derivative thereof. 
     
     
         15 . The method of  claim 14 , wherein the test composition is administered in a dose of at least one microgram of 4-AP or derivative thereof at least once at or near the site of the injured peripheral nerve. 
     
     
         16 . The method of  claim 13 , wherein detecting transient peripheral nerve activity in the presence of the composition comprises one or more of physical examination, electromagnetic fields, functional nerve electrical stimulation, electromyography, or nerve conduction study. 
     
     
         17 . The method of  claim 13 , wherein the test composition is administered systemically to the subject. 
     
     
         18 . The method of  claim 13 , wherein the test composition is administered locally to the site of the peripheral nerve injury. 
     
     
         19 . The method of  claim 13 , wherein the injured peripheral nerve comprises an acute peripheral nerve injury. 
     
     
         20 . The method of  claim 19 , wherein the acute peripheral nerve injury is caused by surgery, trauma, or disease. 
     
     
         21 . The method of  claim 13 , wherein the injured peripheral nerve is selected from the group consisting of a stretched nerve, a pinched nerve, a compressed nerve, a traumatized nerve, and a crushed nerve. 
     
     
         22 . The method of  claim 13 , further comprising administering to the subject one or more treatment agents for treating the peripheral nerve injury after detecting one or more characteristics of transient peripheral nerve activity in the injured peripheral nerve in the presence of the test compound. 
     
     
         23 . The method of  claim 22 , wherein the treatment agent promotes remyelination. 
     
     
         24 . The method of  claim 22 , wherein the treatment agent promotes functional recovery of the peripheral nerve. 
     
     
         25 . The method of  claim 22 , wherein the treatment agent comprises 4-AP or a derivative thereof. 
     
     
         26 . The method of  claim 25 , wherein the treatment agent comprising 4-AP or a derivative thereof is administered at least once daily after determining the peripheral nerve injury has capacity for recovery. 
     
     
         27 . The method of  claim 25 , wherein the 4-AP or a derivative thereof is in the form of a pharmaceutically acceptable salt. 
     
     
         28 . The method of  claim 25 , wherein the treatment agent comprising 4-AP or a derivative thereof comprises a polymer or hydrogel. 
     
     
         29 . The method of  claim 25 , wherein the treatment agent comprising 4-AP or a derivative thereof is administered systemically by injection, oral delivery, transdermal delivery, insertion, or implantation. 
     
     
         30 . The method of  claim 25 , wherein the treatment agent comprising 4-AP or a derivative thereof is administered by insertion, implantation, or injection into the subject at or near the site of the peripheral nerve injury. 
     
     
         31 . The method of  claim 25 , wherein the treatment agent comprising the 4-AP or derivative thereof is administered by a sustained delivery device. 
     
     
         32 . The method of  claim 31 , wherein the sustained delivery device is an implant or osmotic pump. 
     
     
         33 . The method of  claim 32 , wherein the sustained delivery device is an implant and wherein the implant is a nerve cuff. 
     
     
         34 . The method of  claim 32 , wherein the sustained delivery device is an implant and wherein the implant is a bioerodible or reservoir-based implant. 
     
     
         35 . The method of  claim 25 , wherein the treatment agent is erythropoietin or a derivative thereof, forskolin or a derivative thereof, glial growth factor-2, a myelin binding antibody, or any combination thereof.