Treatment of neurological disorders by dsrna administration

Abstract

The present invention relates to methods to treat neurological disorders comprising intrathecal injection of an effective amount of a double-stranded (ds) RNA into a subject in need, wherein said dsRNA inhibits the expression of a target gene and to pharmaceutical compositions useful for such treatment.

1 . A method to treat or ameliorate neurological disorders comprising intrathecal injection of an effective amount of a double-stranded (ds) RNA into a subject in need, wherein said dsRNA inhibits the expression of a target gene.  
     
     
         2 . A method according to  claim 1  wherein said neurological disorder is selected from the group consisting of Alzheimer, Parkinson, multiple sclerosis, schizophrenia, epilepsy, depression and pain.  
     
     
         3 . A method according to  claim 1  wherein said neurological disorder is chronic neuropathic pain.  
     
     
         4 . A method according to  claim 1  wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.  
     
     
         5 . A method according to the preceding claim wherein said target gene is selected from the group consisting of purine receptors P1 or P2, Galanin R1 receptor, IL-24, IL-20Ralpha, IL-20Rbeta, Mob-5 or MMP7.  
     
     
         6 . The method according to the preceding claim wherein said target gene is P 2 X 3  or P 2 X 2  or Mob-5.  
     
     
         7 . A method as in the preceding claim wherein the subject in need is a human.  
     
     
         8 . A method as in  claim 1  wherein the subject in need is a rat.  
     
     
         9 . A method according to the preceding claim wherein at least 200 μg of dsRNA are intrathecally injected.  
     
     
         10 . A method according to the preceding claim wherein the dsRNA comprises a double-stranded region of 15 to 25 nt.  
     
     
         11 . A method according to the preceding claim wherein the dsRNA comprises a 3′ overhang on the antisense or the sense strand, or both strands, of at least one nucleotide.  
     
     
         12 . A method according to  claim 10  wherein the overhang contains at least one modified nucleotide.  
     
     
         13 . A method according to  claim 11  wherein the overhang comprises at least one 2′-MOE modified nucleotide.  
     
     
         14 . A method according to  claim 10  wherein the overhang comprises 4 Uracils.  
     
     
         15 . A method according to according the preceding claims wherein the dsRNA comprises at least one phosphorothioate linkage.  
     
     
         16 . A pharmaceutical composition comprising an effective amount of a double stranded RNA inhibiting the expression of P 2 X 3  or P 2 X 2  in an amount effective to treat chronic pain in a subject in need.  
     
     
         17 . A pharmaceutical composition comprising an effective amount of at least one double stranded RNA, said double stranded RNA comprising a strand of the sequence selected from the group consisting of SEQ ID Nos: 7, 9, 11, 13, 15, 17 and 22.  
     
     
         18 . Use of a double stranded RNA for the preparation of a medicament for the treatment of chronic pain.  
     
     
         19 . The use of  claim 18  wherein the double stranded RNA inhibits purine receptors P1 or P2 or Galanin R1 receptor or IL-24 or IL-20Ralpha or IL-20Rbeta, Mob-5 or MMP7 or P 2 X 3  or P 2 X 2 .  
     
     
         20 . The use of  claim 18  wherein said chronic pain is cancer pain or osteoarthritis pain or allodynia or hyperalgesia.