Methods and compositions for the prevention and treatment of friedreich's ataxia

Abstract

The disclosure provides methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with Friedreich's ataxia, and/or reducing the likelihood or severity of Friedreich's ataxia. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to e.g., reduce oxidative stress, increase mitochondrial metabolism, or a combination thereof.

1 . A method for treating or preventing Friedreich's ataxia or the signs or symptoms of reduced frataxin levels or activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the peptide D-Arg-2′,6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject displays reduced levels of frataxin expression compared to a normal control subject. 
     
     
         3 . The method of  claim 1 , wherein the peptide is administered daily for 6 weeks or more. 
     
     
         4 . The method of  claim 1 , wherein the peptide is administered daily for 12 weeks or more. 
     
     
         5 . The method of  claim 1 , wherein the subject has been diagnosed as having Friedreich's ataxia. 
     
     
         6 . The method of  claim 5 , wherein the Friedreich's ataxia comprises one or more of muscle weakness, loss of coordination, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. 
     
     
         7 . The method of  claim 1 , wherein the subject is human. 
     
     
         8 . The method of  claim 1 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly. 
     
     
         9 . The method of  claim 1 , further comprising separately, sequentially or simultaneously administering to the subject one or more therapeutic agents selected from the group consisting of ACE inhibitors, digoxin, enalapril, or lisinopril, diuretics, beta blockers, idebenone, deferiprone, and insulin. 
     
     
         10 . The method of  claim 1 , wherein the pharmaceutically acceptable salt comprises acetate or trifluoroacetate salt. 
     
     
         11 . A method for reducing mitochondrial iron in a mammalian subject having or suspected of having Friedreich's ataxia, the method comprising: administering to the subject a therapeutically effective amount of the peptide D-Arg-2′,6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 11 , wherein the mammalian subject has decreased expression of frataxin compared to a normal control subject. 
     
     
         13 . The method of  claim 11 , wherein the peptide is administered daily for 6 weeks or more. 
     
     
         14 . The method of  claim 11 , wherein the peptide is administered daily for 12 weeks or more. 
     
     
         15 . The method of  claim 11 , wherein the Friedreich's ataxia comprises one or more of muscle weakness, loss of coordination, motor control impairment, vision impairment, hearing impairment, slurred speech, curvature of the spine, diabetes, and heart disorders. 
     
     
         16 . The method of  claim 11 , wherein the subject is human. 
     
     
         17 . The method of  claim 11 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly 
     
     
         18 . The method of  claim 11 , further comprising separately, sequentially or simultaneously administering to the subject one or more therapeutic agents selected from the group consisting of ACE inhibitors, digoxin, enalapril, or lisinopril, diuretics, beta blockers, idebenone, deferiprone, and insulin. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 9 , wherein the combination of peptide and an additional therapeutic agent has a synergistic effect in the prevention or treatment of Friedreich's ataxia. 
     
     
         21 . The method of  claim 18 , wherein the combination of peptide and an additional therapeutic agent has a synergistic effect in the prevention or treatment of Friedreich's ataxia.