Compositions and method for reducing seizures

Abstract

Provided are compositions and methods for prophylaxis and/or therapy of disorders that involve seizures. The compositions and methods relate to a recombinant adeno-associated virus (rAAV) comprising a I56i enhancer sequence, and a sequence encoding hM3Dq modified muscarinic receptor (Gq-DREADD). The method includes introducing the rAAV into interneurons of an individual such that Gq-DREADD is expressed in interneurons of the individual. The method can further comprise administering to the individual an agonist of the Gq-DREADD, such for reducing or preventing seizures.

What is claimed is: 
     
         1 . A method comprising administering to an individual a recombinant adeno-associated virus (rAAV) comprising: i) a I56i enhancer sequence, and ii) a sequence encoding hM3Dq modified muscarinic receptor (Gq-DREADD), such that the Gq-DREADD is expressed in interneurons of the individual. 
     
     
         2 . The method of  claim 1 , wherein the Gq-DREADD is only expressed in GABA-ergic interneurons in the individual. 
     
     
         3 . The method of  claim 2 , wherein the individual has, is suspected of having, or has been diagnosed with epilepsy. 
     
     
         4 . The method of  claim 2 , further comprising administering to the individual an agonist of the Gq-DREADD. 
     
     
         5 . A method for prophylaxis and/or therapy for seizures in an individual in need thereof, the method comprising introducing into an individual in need thereof a recombinant adeno-associated virus (rAAV) comprising: i) a I56i enhancer sequence, and ii) a sequence encoding hM3Dq modified muscarinic receptor (Gq-DREADD), and subsequently administering to the individual an effective amount of an agonist of the Gq-DREADD such that the severity of the seizures are reduced or the seizures are prevented. 
     
     
         6 . The method of  claim 5 , wherein the individual is experiencing a seizure at time of the administering the agonist of the Gq-DREADD receptor and wherein the severity of the seizure is reduced subsequent to the administering. 
     
     
         7 . The method of  claim 5 , wherein the seizure is selected from a partial seizure or a generalized seizure. 
     
     
         8 . The method of  claim 5 , wherein the individual has, is suspected of having, or has been diagnosed with epilepsy. 
     
     
         9 . The method of  claim 8 , wherein the individual has been diagnosed with pharmaco-resistant epilepsy. 
     
     
         10 . The method of  claim 5 , wherein the Gq-DREADD is only expressed in GABA-ergic interneurons in the individual. 
     
     
         11 . An expression vector or adeno-associated virus (rAAV) comprising i) a I56i enhancer sequence, and ii) a sequence encoding hM3Dq modified muscarinic receptor (Gq-DREADD). 
     
     
         12 . The rAAV of  claim 5 , wherein the rAAV is present in a pharmaceutical formulation.