Antisense Oligonucleotides Against Neutral Sphingomyelinase and Neutral Sphingomyelinase Inhibitor GW4869 for Degenerative Neurological Disorders

Abstract

Alzheimer's disease (AD) is the most common human neurodegenerative disease of the CNS resisting in progressive neuronal death and memory loss. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. It was discovered that antisense oligonucleotide against neutral sphingomyelinase and GW 4889, a chemical inhibitor of neutral sphingomyelinase, inhibit activation of glial cells and protect neurons in AD cell culture and animal models. These results suggest the following new treatment options for AD patients: Antisense oligonucleotide against neutral sphingomyelinase and GW 4889.

1 . A composition for the treatment of a neurodegenerative disorder, the composition comprising:
 an inhibitor of neutral sphingomyelinase, the inhibitor comprising:
 an antisense oligonucleotide against neutral sphingomyelinase or GW4869 or an antisense oligonucleotide against neutral sphingomyelinase and GW4869. 
   
     
     
         2 . The composition of  claim 1  wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease and combinations thereof. 
     
     
         3 . The composition of  claim 1 , wherein the antisense oligonucleotide is selected from SEQ. ID. NO. 12 and SEQ. ID. NO. 18. 
     
     
         4 . The composition of  claim 1 , wherein the inhibitor of neutral sphingomyelinase comprises the antisense oligonucleotide against neutral sphingomyelinase and GW4889. 
     
     
         5 . The composition of  claim 4 , wherein the antisense oligonucleotide is selected from SEQ. ID. NO. 12 and SEQ. ID. NO. 16. 
     
     
         6 . The composition of  claim 1 , wherein the inhibitor of neutral sphingomyelinase comprises the antisense oligonucleotide against neutral sphingomyelinase. 
     
     
         7 . The composition of  claim 6 , wherein the antisense oligonucleotide is selected from SEQ. ID. NO. 12 and SEQ. ID. NO. 18. 
     
     
         8 . A method of treating neurodegenerative disorders in a mammal in need thereof, the method comprising:
 administering a composition of  claim 1  comprising an inhibitor of neutral sphingomyelinase to the mammal in need thereof to treat the neurodegenerative disorder.   
     
     
         9 . The method of  claim 8 , wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease and combinations thereof. 
     
     
         10 . The method of  claim 8 , wherein the inhibitor of neutral sphingomyelinase comprises the antisense oligonucleotide against neutral sphingomyelinase. 
     
     
         11 . The method of  claim 8 , wherein the antisense oligonucleotide is selected from SEQ. ID, NO. 12 and SEQ. ID. NO. 16. 
     
     
         12 . The method of  claim 10 , wherein the antisense oligonucleotide is selected from SEQ. ID. NO. 12 and SEQ. ID. NO, 16.