Compositions And Methods For The Treatment Of Neurologic And Psychiatric Conditions

Abstract

The invention provides pharmaceutical compositions and methods of use thereof for preventing or ameliorating disorders of the nervous system. More specifically, the invention provides pharmaceutical compositions, including phosphopeptides, that when administered disrupt TrkB-mediated activation of PLCγ1 phosphorylation. The invention further provides method of treatment comprising administering inhibitors of TrkB-mediated activation of PLCγ1 phosphorylation alone or in combination with other pharmaceutical compositions to prevent or ameliorate nervous system disorders such as epilepsy, stroke, anxiety, migraine, and pain.

1 .- 18 . (canceled) 
     
     
         19 . A method of treating or ameliorating a disorder of the nervous system in a subject comprising administering to said subject a therapeutically effective amount of an interfering molecule, wherein said interfering molecule inhibits TrkB-mediated activation of PLCγ1. 
     
     
         20 . A method for preventing onset or limiting the progression of a disorder of the nervous system in a subject comprising administering to said subject a therapeutically effective amount of an interfering molecule inhibits TrkB-mediated activation of PLCγ1. 
     
     
         21 . The method according to any one of  claims 19 - 20 , wherein said disorder of the nervous system is selected from the group consisting of stroke, anxiety, epilepsy, head trauma, migraine, pain, schizophrenia, affective disorders, addiction, and combinations thereof. 
     
     
         22 . The method according to  claim 21 , wherein said disorder of the nervous system comprises epilepsy. 
     
     
         23 . The method according to any of  claims 19 - 20 , wherein said subject is a mammal. 
     
     
         24 . The method according to  claim 23 , wherein said subject is a human. 
     
     
         25 . The method according to any of  claims 19 - 20 , wherein said interfering molecule is selected from the group consisting of a polypeptide, phosphopepetide, peptide fragment, antibody, an antisense RNA, a dominant negative form of PLCγ1 and combination thereof. 
     
     
         26 . The method according to  claim 25 , wherein said interfering molecule is a small molecule capable of permeating the blood brain barrier. 
     
     
         27 . The method according to  claim 25 , wherein said interfering molecule is polypeptide capable of permeating the blood brain barrier. 
     
     
         28 . The method according to  claims 19 - 20 , wherein the interfering molecule is a phosphopeptide comprising the sequence YGRKKRRQRRRLQNLAKASPVpYLDI (SEQ ID NO: 3), wherein Y816 is phosphorylated (designated by p). 
     
     
         29 . The method according to  claim 27 , wherein the phosphopeptide is comprising the sequence YGRKKRRQRRRLQNLAKASPVpYLDI (SEQ ID NO: 3), wherein Y816 is phosphorylated (designated by p).