Compositions And Methods For Treating Traumatic Brain Injury

Abstract

The present invention relates, in certain embodiments, to methods for preventing and/or treating neurodegenerative damage (e.g., secondary cascade of neurodegenerative damage) and improving functional outcomes (e.g., outcomes associated with cognitive, behavior and sensorimotor function) caused by traumatic brain injury (TBI) using neuroprotective lipoyl compounds. The present invention also provides, in various embodiments, compositions for use in treating and/or preventing TBI in a subject in need thereof, compounds for use in the manufacture of a medicament for treating and/or preventing TBI in a subject in need thereof, and methods of preparing a pharmaceutical composition for treating and/or preventing secondary brain damage caused by TBI.

1 - 15 . (canceled) 
     
     
         16 . A method for treating traumatic brain injury in a subject in need thereof, comprising administering to the subject an effective amount of a compound of the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the compound or pharmaceutically acceptable salt thereof is administered to the subject orally or intravenously. 
       
     
     
         17 . The method of  claim 16 , comprising administering to the subject an effective amount of the compound, or a composition comprising the compound, and a pharmaceutically acceptable carrier. 
     
     
         18 . The method of  claim 16 , comprising administering to the subject an effective amount of a pharmaceutically acceptable salt of the compound, or a composition comprising the pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier. 
     
     
         19 . The method of  claim 18 , wherein the pharmaceutically acceptable salt comprises a monovalent cation or a divalent cation. 
     
     
         20 . The method of  claim 19 , wherein the monovalent cation is a monovalent metal cation and the divalent cation is a divalent metal cation. 
     
     
         21 . The method of  claim 18 , wherein the pharmaceutically acceptable salt comprises a sodium ion. 
     
     
         22 . The method of  claim 16 , wherein the compound or pharmaceutically acceptable salt thereof is administered to the subject in a composition comprising a pharmaceutically acceptable carrier or diluent. 
     
     
         23 . The method of  claim 22 , wherein the compound or pharmaceutically acceptable salt thereof is at least 90% enantiomerically pure in the composition. 
     
     
         24 . The method of  claim 16 , wherein the compound or pharmaceutically acceptable salt thereof has a percent optical purity by weight of at least 99%. 
     
     
         25 . The method of  claim 16 , wherein the subject is a human. 
     
     
         26 . The method of  claim 16 , wherein the compound or pharmaceutically acceptable salt hereof is administered to the subject orally. 
     
     
         27 . The method of  claim 16 , wherein the compound or pharmaceutically acceptable salt thereof is administered to the subject intravenously. 
     
     
         28 . The method of  claim 16 , wherein the method is a method for treating neurodegenerative damage caused by traumatic brain injury. 
     
     
         29 . The method of  claim 28 , wherein the neurodegenerative damage affects the hippocampus region of the brain. 
     
     
         30 . The method of  claim 29 , wherein the neurodegenerative damage to the hippocampus region of the brain affects cognitive function associated with learning and memory. 
     
     
         31 . The method of  claim 28 , wherein the neurodegenerative damage affects sensorimotor function. 
     
     
         32 . The method of  claim 28 , wherein the neurodegenerative damage is associated with a focal or diffused traumatic brain injury. 
     
     
         33 . The method of  claim 28 , wherein the neurodegenerative damage is secondary damage at a site other than the site of the primary lesion. 
     
     
         34 . A method for inhibiting the generation of mitochondrial reactive oxygen species (mtROS) in the brain of a subject in need thereof, comprising administering to the subject an effective amount of a compound of the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         35 . A method for improving mitochondrial bioenergetics in the brain of a subject in need thereof, comprising administering to the subject an effective amount of a compound of the following structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.