Inhibition of let7i as a means to enhance the protective effect of progesterone against stroke

Abstract

The subject invention provides methods of treating neurological disease or disorder, such as brain injuries, such as stroke, traumatic brain injury (TBI), or other ischemic events that cause brain injury by inhibiting or down-regulating Let-7i activity or function. The disclosed methods may have the potential to extend the “window of opportunity” for treatment of such injuries and enhance the effectiveness of existing therapeutics.

We claim: 
     
         1 . A method of treating a neurological disease or disorder comprising administering one or more antagonist of Let-7i or a composition comprising said Let-7i antagonist to a subject having a neurological disease or disorder. 
     
     
         2 . The method according to  claim 1 , wherein the neurological disease or disorder is selected from: severance of nerves or nerve damage, severance of cerebrospinal nerve cord (CNS), damage to brain or nerve cells, traumatic brain injury, spinal cord injury, hypoxia, ischemia, brain injury, diabetic neuropathy, peripheral neuropathy, aging, neurodegenerative disease, or peripheral nerve injury. 
     
     
         3 . The method according to  claim 2 , wherein said neurological disease or disorder is aging of the nervous system or an age-associated neurodegenerative disease. 
     
     
         4 . The method according to  claim 3 , wherein said aging of the nervous system comprises one or more of the following: (a) changes in memory, (b) alterations of language function, (c) visual-perceptual changes, (d) slowing of reaction time, and/or (f) decreased balance and coordination. 
     
     
       5. The method according to  claim 1 , wherein said antagonist of Let-7i is an antisense oligonucleotide, siRNA, shRNA, or interfering RNA that down-regulates Let-7i activity or function. 
     
     
         6 . The method according to  claim 1 , said method further comprising the administration of progesterone or a composition thereof to said subject. 
     
     
         7 . The method according to  claim 1 , said method further comprising the administration of BDNF or a composition thereof to said subject. 
     
     
         8 . The method according to  claim 6 , wherein said antagonist of Let-7i or composition thereof and/or said progesterone or a composition thereof is/are administered separately, concurrently, or as a single composition. 
     
     
         9 . The method according to  claim 7 , wherein said antagonist of Let-7i or a composition thereof and/or said BDNF or composition thereof is/are administered separately, concurrently, or as a single composition.