Impaired energy processing disorders and mitochondrial deficiency

Abstract

Some aspects of the invention provide for a method of treating Impaired Energy Processing Disorders and Mitochondrial Deficiencies using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.

1 .- 15 . (canceled) 
     
     
         16 . A method of treating or inhibiting progression of impaired energy processing disorder or mitochondrial deficiency, comprising:
 repeatedly administering an effective amount of a deuterated polyunsaturated fatty acid or fatty acid ester to a patient;   wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 1% to about 99% of the total amount of polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient; and   wherein the deuterated polyunsaturated fatty acid or fatty acid ester is arachidonic acid, an arachidonic acid ester, eicosapentaenoic acid, an eicosapentaenoic acid ester, docosahexaenoic acid, a docosahexaenoic acid ester, linoleic acid, a linoleic acid ester, linolenic acid, or a linolenic acid ester.   
     
     
         17 . The method of  claim 16 , wherein the impaired energy processing disorder or mitochondrial deficiency is selected from: Co-enzyme Q deficiency; Diabetes mellitus and deafness (DAD); Maternally Inherited Diabetes and Deafness (MIDD); Friedreich's ataxia (FA); Leber's congenital amaurosis; Leber's hereditary optic neuropathy (LHON); Leigh syndrome; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome; Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE); Myoclonus Epilepsy Associated with Ragged-Red Fibers (MERRF) syndrome; Myoneurogenetic gastrointestinal encephalopathy (MNGIE) and neuropathy; Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP); Wolff-Parkinson-White syndrome; X-linked Adrenoleukodystrophy (X-ALD), Fanconi's syndrome and Pearson's syndrome. 
     
     
         18 . The method of  claim 17 , wherein the impaired energy processing disorder or mitochondrial deficiency is Friedreich's ataxia. 
     
     
         19 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is deuterated at a level greater than 0.02%. 
     
     
         20 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 1% and 50% of the total amount of fatty acids or fatty acid esters administered to or ingested by the patient. 
     
     
         21 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 1% and 30% of the total amount of fatty acids or fatty acid esters administered to or ingested by the patient. 
     
     
         22 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient comprises between about 20% and 50% of the total amount of fatty acids or fatty acid esters administered to or ingested by the patient. 
     
     
         23 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is arachidonic acid. 
     
     
         24 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is an arachidonic acid ester. 
     
     
         25 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is docosahexaenoic acid. 
     
     
         26 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is a docosahexaenoic acid ester. 
     
     
         27 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is linoleic acid. 
     
     
         28 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is a linoleic acid ester. 
     
     
         29 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is linolenic acid. 
     
     
         30 . The method of  claim 16 , wherein the deuterated fatty acid or fatty acid ester is a linolenic acid ester. 
     
     
         31 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of 11,11-D2-linolenic acid, 14,14-D2-linolenic acid, 11,11,14,14-D4-linolenic acid, 11,11-D2-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, and 11-D-linoleic acid. 
     
     
         32 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of a 11,11-D2-linolenic acid ester, a 14,14-D2-linolenic acid ester, a 11,11,14,14-D4-linolenic acid ester, a 11,11-D2-linoleic acid ester, a 11-D-linolenic acid ester, a 14-D-linolenic acid ester, a 11,14-D2-linolenic acid ester, and a 11-D-linoleic acid ester. 
     
     
         33 . The method of  claim 16 , wherein the ester is a triglyceride, diglyceride, or monoglyceride. 
     
     
         34 . The method of  claim 16 , further comprising co-administering an antioxidant. 
     
     
         35 . The method of  claim 34 , wherein the antioxidant is idebenone, mitoquinone, mitoquinol, vitamin C, or vitamin E. 
     
     
         36 . The method of  claim 16 , wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 0.1 mg/kg to 100 mg/kg per day. 
     
     
         37 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid. 
     
     
         38 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid ethyl ester. 
     
     
         39 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11,14,14-D4-linolenic acid. 
     
     
         40 . The method of  claim 16 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11,14,14-D4-linolenic acid ethyl ester.