Use of myostatin inhibitors and combination therapies

Abstract

The present disclosure relates to the treatment of muscle conditions, such as SMA, with the use of an agent that inhibits myostatin signaling. The disclosure includes combination therapies that include a myostatin inhibitor and a neuronal corrector.

1 - 26 . (canceled) 
     
     
         27 . A method of treating spinal muscular atrophy (SMA) in a subject, the method comprising:
 (i) selecting a subject, wherein the subject has SMA and has been genetically identified as having a mutation in a survival motor neuron 1 (SMN1) gene; and   (ii) administering to the subject a selective myostatin inhibitor and an SMN corrector therapy in amounts effective to treat SMA.   
     
     
         28 . The method of  claim 27 , wherein the subject has been determined to have two or more copies of a survival motor neuron 2 (SMN2) gene. 
     
     
         29 . The method of  claim 27 , wherein the SMN corrector therapy comprises an agent capable of increasing or improving SMN gene expression, SMN protein production, and/or functional SMN activity. 
     
     
         30 . The method of  claim 27 , wherein the SMN corrector therapy comprises a splice modifier, an SMN gene replacement or gene therapy, an SMN transcription enhancer, an SMN protein translation enhancer, or an SMN protein stabilizer. 
     
     
         31 . The method of  claim 27 , wherein the myostatin inhibitor inhibits cleavage of a myostatin prodomain, inhibits release of a mature myostatin growth factor, and/or inhibits activation of a pro and latent myostatin to a mature myostatin. 
     
     
         32 . The method of  claim 27 , wherein the SMA is type I SMA, type II SMA, or type III SMA. 
     
     
         33 . The method of  claim 27 , wherein the mutation in an SMN1 gene has been identified by genetic screening carried out in a newborn/infant subject or in utero. 
     
     
         34 . The method of  claim 27 , wherein the subject is a pediatric subject or a young adult who is still growing and anabolically active. 
     
     
         35 . The method of  claim 27 , wherein the myostatin inhibitor and the SMN corrector therapy are administered concurrently or within six months of one another. 
     
     
         36 . A method of treating spinal muscular atrophy (SMA) in a subject, the method comprising:
 (i) selecting a subject, wherein the subject: (a) has SMA and has been genetically identified as having a mutation in an SMN1 gene; and (b) is on an SMN corrector therapy; and   (ii) administering to the subject a selective myostatin inhibitor in an amount effective to treat SMA.   
     
     
         37 . The method of  claim 36 , wherein the subject has been determined to have two or more copies of an SMN2 gene. 
     
     
         38 . The method of  claim 36 , wherein the SMN corrector therapy comprises an agent capable of increasing or improving SMN gene expression, SMN protein production, and/or functional SMN activity. 
     
     
         39 . The method of  claim 36 , wherein the SMN corrector therapy comprises a splice modifier, an SMN gene replacement or gene therapy, an SMN transcription enhancer, an SMN protein translation enhancer, or an SMN protein stabilizer. 
     
     
         40 . The method of  claim 36 , wherein the myostatin inhibitor inhibits cleavage of a myostatin prodomain, inhibits release of a mature myostatin growth factor, and/or inhibits activation of a pro and latent myostatin to a mature myostatin. 
     
     
         41 . The method of  claim 36 , wherein the SMA is type I SMA, type II SMA, or type III SMA. 
     
     
         42 . The method of  claim 36 , wherein the mutation in an SMN1 gene has been identified by genetic screening carried out in a newborn/infant subject or in utero. 
     
     
         43 . The method of  claim 36 , wherein the subject is a pediatric subject or a young adult who is still growing and anabolically active. 
     
     
         44 . The method of  claim 36 , wherein the selective myostatin inhibitor is administered in an amount effective to prevent or reduce muscle atrophy. 
     
     
         45 . A method of treating ambulatory SMA in a subject, the method comprising:
 (i) selecting a subject, who has been genetically identified as having a mutation in an SMN1 gene; and   (ii) administering to the subject a selective myostatin inhibitor in an amount effective to treat ambulatory SMA.   
     
     
         46 . The method of  claim 45 , wherein the ambulatory SMA is type III SMA. 
     
     
         47 . The method of  claim 45 , wherein the selective myostatin inhibitor is administered in an amount effective to prevent or reduce muscle atrophy. 
     
     
         48 . The method of  claim 45 , wherein the subject has been determined to have two or more copies of an SMN2 gene. 
     
     
         49 . The method of  claim 45 , wherein the myostatin inhibitor inhibits cleavage of a myostatin prodomain, inhibits release of a mature myostatin growth factor, and/or inhibits activation of a pro and latent myostatin to a mature myostatin. 
     
     
         50 . The method of  claim 45 , wherein the mutation in an SMN1 gene has been identified by genetic screening carried out in a newborn/infant subject or in utero. 
     
     
         51 . The method of  claim 45 , wherein the subject is a pediatric subject or a young adult who is still growing and anabolically active. 
     
     
         52 . The method of  claim 45 , wherein the subject is not on an SMN corrector therapy. 
     
     
         53 . The method of  claim 27 , wherein the subject is a pediatric subject. 
     
     
         54 . The method of  claim 36 , wherein the subject is a pediatric subject.