Treatment for spinal muscular atrophy

Abstract

A method of treating spinal muscular atrophy. The method includes administering an effective amount of composition including a sodium-proton exchanger inhibitor and a pharmaceutically acceptable carrier or salt, to a subject with spinal muscular atrophy to ameliorate a symptom of spinal muscular atrophy.

1 . A method for modulating SMN gene expression in a cell, comprising contacting an effective amount of sodium-proton exchanger inhibitor to the cell, to increase the expression level of SMN exon 7 in the cell. 
     
     
         2 . The method as claimed in  claim 1 , wherein the sodium-proton exchanger inhibitor is 5-(N-ethyl-N-isopropyl)-amiloride. 
     
     
         3 . The method as claimed in  claim 1 , wherein the cell is a human cell. 
     
     
         4 . The method as claimed in  claim 1 , wherein the cell is within a mammal. 
     
     
         5 . The method as claimed in  claim 1 , wherein the sodium-proton exchanger inhibitor induces the expression of SRp20 protein and increases the number of nuclear gems. 
     
     
         6 . The method as claimed in  claim 1 , wherein the ratio of SMN transcripts having exon 7 to those lacking exon 7 is increased by at least 50%. 
     
     
         7 . A method for modulating SMN gene expression in a subject, comprising administering to a subject an effective amount of a sodium-proton exchanger inhibitor to increase the expression level of SMN exon 7 in a cell of the subject. 
     
     
         8 . The method as claimed in  claim 7 , wherein the sodium-proton exchanger inhibitor is 5-(N-ethyl-N-isopropyl)-amiloride. 
     
     
         9 . The method as claimed in  claim 7 , wherein the subject is a mammal. 
     
     
         10 . The method as claimed in  claim 7 , wherein the ratio of SMN transcripts having exon 7 to those lacking exon 7 is increased by at least 50%. 
     
     
         11 . A method of treating spinal muscular atrophy, comprising administering an effective amount of composition comprising a sodium-proton exchanger inhibitor and a pharmaceutically acceptable carrier or salt, to a subject with spinal muscular atrophy to ameliorate a symptom of spinal muscular atrophy. 
     
     
         12 . The method as claimed in  claim 11 , wherein the sodium-proton exchanger inhibitor is 5-(N-ethyl-N-isopropyl)-amiloride. 
     
     
         13 . The method as claimed in  claim 11 , wherein the composition is further administered in combination with a second agent comprising histone deacetylase inhibitor, hydroxyurea, anthracycline antibiotic, phosphatase inhibitor, nonsteroidal anti-inflammatory drug, cyclooxygenase inhibitor, tobramycin, amikacin, ribonucleotide reductase inhibitor, or cell cycle inhibitor. 
     
     
         14 . The method as claimed in  claim 13 , wherein the histone deacetylase inhibitor is a butyrate, valproic acid, M344, SAHA, trapoxin, or trichostatin A. 
     
     
         15 . The method as claimed in  claim 13 , wherein the composition and the second agent are systemically or topically administered simultaneously or sequentially. 
     
     
         16 . The method as claimed in  claim 11 , wherein the subject is a mammal. 
     
     
         17 . The method as claimed in  claim 11 , wherein the subject is a fetus, and the composition is administered to the subject in utero. 
     
     
         18 . The method as claimed in  claim 11 , wherein the subject is homozygous for mutations in SMN1. 
     
     
         19 . The method as claimed in  claim 11 , wherein the symptom comprises muscular paralysis, muscular atrophy, decreased expression of SMN exon 7 in a cell of the subject, or walking gait.