Neurodegenerative disorders and muscle diseases implicating pufas

Abstract

Some aspects of the invention provide for a method of treating Alzheimer's Disease, Mild Cognitive Impairment, Frontotemperal Dementia, Amyotrophic Lateral Sclerosis and/or Multiple Sclerosis 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.

What is claimed is: 
     
         1 . A method of treating or preventing the progression of Alzheimer's Disease, Mild Cognitive Impairment, or Frontotemperal Dementia, comprising:
 administering an effective amount of a polyunsaturated substance to a patient in need thereof, wherein the polyunsaturated substance is chemically modified such that one or more bonds is stabilized against oxidation;   wherein the polyunsaturated substance or a polyunsaturated metabolite thereof comprising said one or more stabilized bonds is incorporated into the patient's body following administration.   
     
     
         2 . The method of  claim 1 , wherein the polyunsaturated substance is a fatty acid, a fatty acid mimetic, or a fatty acid pro-drug. 
     
     
         3 . The method of  claim 2 , wherein the fatty acid, fatty acid mimetic, or fatty acid pro-drug is stabilized at one or more bis-allylic positions. 
     
     
         4 . The method of  claim 3 , wherein the stabilization comprises at least one  13 C atom or at least one deuterium atom at a bis-allylic position, wherein the at least one  13 C atom or the at least one deuterium atom is present at a level significantly above the naturally-occurring abundance level of said isotope. 
     
     
         5 . The method of  claim 4 , wherein the stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise between about 10% and 50% of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         6 . The method of  claim 4 , wherein the isotopically stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise between about 10% and 30% of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         7 . The method of  claim 4 , wherein the isotopically stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise about 20% or more of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         8 . The method of  claim 4 , wherein a cell or tissue of the patient maintains a sufficient concentration of the fatty acid, fatty acid mimetic, or fatty acid pro-drug to prevent autooxidation of the naturally occurring polyunsaturated fatty acid, mimetic, or ester pro-drug. 
     
     
         9 . The method of  claim 4 , wherein the polyunsaturated substance is an omega-3 fatty acid, fatty acid mimetic, or fatty acid pro-drug, or an omega-6 fatty acid, fatty acid mimetic, or fatty acid pro-drug. 
     
     
         10 . The method of  claim 9 , wherein the polyunsaturated substance 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, 14,14-D2-linoleic acid, 11,11,14,14-D4-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, 11-D-linoleic acid, 14-D-linoleic acid, and 11,14-D2-linoleic acid. 
     
     
         11 . The method of  claim 9 , wherein the polyunsaturated substance is further stabilized at a pro-bis-allylic position. 
     
     
         12 . The method of  claim 4 , wherein the polyunsaturated substance is a fatty acid pro-drug ester. 
     
     
         13 . The method of  claim 12 , wherein the ester is a triglyceride, diglyceride, or monoglyceride. 
     
     
         14 . The method of  claim 2  further comprising co-administering an antioxidant. 
     
     
         15 . The method of  claim 14 , wherein the antioxidant is Coenzyme Q, idebenone, mitoquinone, mitoquinol, vitamin C, or vitamin E. 
     
     
         16 . A method of treating or inhibiting the progression of neuromuscular disease, comprising:
 administering an effective amount of a polyunsaturated substance to an Amyotrophic Lateral Sclerosis or Multiple Sclerosis patient in need of treatment, wherein the polyunsaturated substance is chemically modified such that one or more bonds are stabilized against oxidation;   wherein the polyunsaturated substance or a polyunsaturated metabolite thereof comprising said one or more stabilized bonds is incorporated into the patient's body following administration.   
     
     
         17 . The method of  claim 16 , wherein the polyunsaturated substance is a fatty acid, a fatty acid mimetic, or a fatty acid pro-drug. 
     
     
         18 . The method of  claim 17 , wherein the fatty acid, fatty acid mimetic, or fatty acid pro-drug is stabilized at one or more bis-allylic positions. 
     
     
         19 . The method of  claim 18 , wherein the stabilization comprises at least one  13 C atom or at least one deuterium atom at a bis-allylic position, wherein the at least one  13 C atom or the at least one deuterium atom is present at a level significantly above the naturally-occurring abundance level of said isotope. 
     
     
         20 . The method of  claim 19 , wherein the stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise between about 10% and 50% of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         21 . The method of  claim 19 , wherein the isotopically stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise between about 10% and 30% of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         22 . The method of  claim 19 , wherein the isotopically stabilized fatty acid, fatty acid mimetic, or fatty acid pro-drug comprise about 20% or more of the total amount of fatty acids, fatty acid mimetics, or fatty acid pro-drugs administered to the patient. 
     
     
         23 . The method of  claim 19 , wherein a cell or tissue of the patient maintains a sufficient concentration of the fatty acid, fatty acid mimetic, or fatty acid pro-drug to prevent autooxidation of the naturally occurring polyunsaturated fatty acid, mimetic, or ester pro-drug. 
     
     
         24 . The method of  claim 19 , wherein the polyunsaturated substance is an omega-3 fatty acid, fatty acid mimetic, or fatty acid pro-drug, or an omega-6 fatty acid, fatty acid mimetic, or fatty acid pro-drug. 
     
     
         25 . The method of  claim 24 , wherein the polyunsaturated substance 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, 14,14-D2-linoleic acid, 11,11,14,14-D4-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, 11-D-linoleic acid, 14-D-linoleic acid, and 11,14-D2-linoleic acid. 
     
     
         26 . The method of  claim 24 , wherein the polyunsaturated substance is further stabilized at a pro-bis-allylic position. 
     
     
         27 . The method of  claim 19 , wherein the polyunsaturated substance is a fatty acid pro-drug ester. 
     
     
         28 . The method of  claim 27 , wherein the ester is a triglyceride, diglyceride, or monoglyceride. 
     
     
         29 . The method of  claim 17  further comprising co-administering an antioxidant. 
     
     
         30 . The method of  claim 29 , wherein the antioxidant is Coenzyme Q, idebenone, mitoquinone, mitoquinol, vitamin C, or vitamin E.