Mouse model and treatment of hereditary inclusion body myopathy

Abstract

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating myopathy in a subject harboring one or more mutations in the gene encoding a bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), comprising orally administering to the subject a composition comprising an effective amount of sialic acid or a pharmaceutically acceptable salt or prodrug thereof. 
     
     
         22 . The method of  claim 21 , wherein the subject harbors a M712T mutation in GNE. 
     
     
         23 . The method of  claim 21 , wherein subsequent to the administration of the composition, the subject experiences an improvement in a criterion selected from the group consisting of muscle movement, limb movement, muscle growth, muscle stamina, muscle fatigability, muscle strength, muscle tensile force, muscle atrophy, neuronal atrophy, life-span, and extent of activity. 
     
     
         24 . The method of  claim 21 , wherein administration of the composition results in enhanced muscle strength in the subject compared to a subject receiving placebo. 
     
     
         25 . The method of  claim 21 , wherein administration of the composition results in enhanced limb movement in the subject compared to a subject receiving placebo. 
     
     
         26 . The method of  claim 21 , wherein the subject is identified as harboring a mutation in the gene encoding GNE prior to administration of the composition. 
     
     
         27 . A method of treating myopathy in a subject, wherein the method comprises:
 identifying one or more mutations in the gene encoding a bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) in a subject; and   orally administering to the subject a composition comprising an effective amount of sialic acid or a pharmaceutically acceptable salt or prodrug thereof.   
     
     
         28 . The method of  claim 27 , wherein the subject is identified to harbor a M712T mutation in GNE. 
     
     
         29 . The method of  claim 27 , wherein subsequent to the administration of the composition, the subject experiences an improvement in a criterion selected from the group consisting of muscle movement, limb movement, muscle growth, muscle stamina, muscle fatigability, muscle strength, muscle tensile force, muscle atrophy, neuronal atrophy, life-span, and extent of activity. 
     
     
         30 . The method of  claim 27 , wherein administration of the composition results in enhanced muscle strength in the subject compared to a subject receiving placebo. 
     
     
         31 . The method of  claim 27 , wherein administration of the composition results in enhanced limb movement in the subject compared to a subject receiving placebo.