Methods for the treatment of mitochondrial disease

Abstract

The disclosure provides methods of preventing, ameliorating or treating disruption of mitochondrial function and symptoms thereof. The methods provide administering aromatic-cationic peptides in effective amounts to prevent, treat or ameliorate the disruption of mitochondrial oxidative phosphorylation in a cell such as that found in a subject suffering from, or predisposed to a mitochondrial disease or disorder. In some embodiments, the methods comprise administering to a subject suffering from, or at risk for a mitochondrial disease or disorder, an effective amount of an aromatic-cationic peptide to subjects in need thereof.

1 .- 20 . (canceled) 
     
     
         21 . A method for treating mitochondrial disease, disorder or conditions associated with a POLG gene mutation in a subject in need thereof, the method comprising: administering a therapeutically effective amount of peptide D-Arg-2′,6′-Dmt-Lys-Phe-NH2 or a pharmaceutically acceptable salt thereof and thereby treating or ameliorating at least one symptom of the mitochondrial disease, disorder or condition. 
     
     
         22 . The method of  claim 21 , wherein treatment reduces disruption in mitochondrial oxidative phosphorylation of the subject. 
     
     
         23 . The method of  claim 22 , wherein disruption in mitochondrial oxidative phosphorylation in the subject results from impairment of the complete assembly of at least one mitochondrial complex selected from the group consisting of: Complex I; Complex II; Complex III; Complex IV; and Complex V. 
     
     
         24 . The method of  claim 21 , wherein treatment reduces or ameliorates one or more symptoms selected from the group consisting of poor growth, neurological deficit, seizures, autism, autistic spectrum, autistic-like features, learning disabilities, gastrointestinal disorders, severe constipation, diabetes, increased risk of infection, thyroid dysfunction, adrenal dysfunction, autonomic dysfunction, confusion, disorientation, memory loss, poor growth, failure to thrive, poor coordination, sensory (vision, hearing) problems, reduced mental functions, disease of the organ, dementia, respiratory problems, hypoglycemia, apnea, lactic acidosis, seizures, swallowing difficulties, developmental delays, movement disorders (dystonia, muscle spasms, tremors, chorea), stroke, and brain atrophy. 
     
     
         25 . The method of  claim 21 , wherein treatment reduces or ameliorates one or more symptoms selected from the group consisting of loss of muscle coordination or muscle weakness. 
     
     
         26 . The method of  claim 21 , wherein treatment reduces or ameliorates one or more symptoms selected from the group consisting of heart disease, liver disease or kidney disease. 
     
     
         27 . The method of  claim 21 , where in the peptide is formulated as a hydrochloride salt. 
     
     
         28 . The method of  claim 21 , wherein the peptide is administered subcutaneously. 
     
     
         29 . The method of  claim 21 , wherein the peptide is administered orally, topically, systematically, intravenously, intraperitoneally, or intramuscularly. 
     
     
         30 . The method of  claim 21 , wherein the mitochondrial disease or disorder is progressive external ophthalmolplegia (PEO), Alper's disease or sensory ataxia neuropathy with dysarthria and ophthalmoparesis (SANDO).