Glycogen or polysaccharide storage disease treatment method

Abstract

A method for treating glycogen storage disease by administering an effective amount of a composition that includes ketogenic odd carbon fatty acids that ameliorate the symptoms of these diseases.

What is claimed is: 
     
         1 . A pharmaceutical composition for treating a glycogen storage disease comprising:
 a pharmaceutically effective amount of an odd carbon fatty acid that is at least partially water-soluble for the treatment of the glycogen storage disease.   
     
     
         2 . The composition of  claim 1 , further comprising a carrier. 
     
     
         3 . The composition of  claim 1 , further comprising a diluent. 
     
     
         4 . The composition of  claim 1 , further comprising a lipophilic diluent. 
     
     
         5 . The composition of  claim 1 , further comprising an emulsifier. 
     
     
         6 . The composition of  claim 1 , further comprising an emulsifier is selected from the group consisting of Imwitor 370, Imwitor 375, Imwitor 377, Imwitor 380 and Imwitor 829. 
     
     
         7 . The composition of  claim 1 , wherein the odd carbon fatty acid is unneutralized. 
     
     
         8 . The composition of  claim 1 , wherein the odd carbon fatty acid comprises C15, C7, C5 and mixtures or combinations thereof. 
     
     
         9 . The composition of  claim 1 , wherein the odd carbon fatty acid comprises 3-hydroxypentanoate, 3-ketopentanoate and mixtures and combinations thereof. 
     
     
         10 . The composition of  claim 1 , wherein the patient is suspected of having a Type II Glycogen Storage Disease. 
     
     
         11 . The composition of  claim 1 , wherein the patient is suspected of having Pompe's disease. 
     
     
         12 . The composition of  claim 1 , wherein the patient is suspected of having an anapleurotic disease. 
     
     
         13 . The composition of  claim 1 , wherein the odd carbon fatty acid is adapted for a dosage of between 1 to 2 gr/kg/day. 
     
     
         14 . The composition of  claim 1 , wherein the odd carbon fatty acid comprises an acid value of 0.1 or less mg KOH/gr, a hydroxyl value of 2.8 or less mg KOH/gr. 
     
     
         15 . The composition of  claim 1 , wherein the odd carbon fatty acid has a purity of at least about 98 percent. 
     
     
         16 . The composition of  claim 1 , wherein the odd carbon fatty acid comprises triheptanoate that is at least about 97% pure. 
     
     
         17 . A method of treating a patient suffering from Pompe's disease comprising the steps of:
 administering to a patient in need thereof a composition comprising a human recombinant α-glucosidase in a pharmaceutically acceptable carrier, in an amount insufficient to treat the disease; and   concurrently providing the patient with a pharmaceutically effective amount of an odd carbon fatty acid to reduce the amount of the recombinant α-glucosidase necessary to treat the patient.   
     
     
         18 . The method of  claim 17 , wherein the composition is administered in an amount of from about 0.01 to about 100 milligrams of human recombinant α-glucosidase per 100 kilograms of patient per month. 
     
     
         19 . The method of  claim 17 , wherein the α-glucosidase and pharmaceutically effective amount of an odd carbon fatty acid are provided in a single-dose. 
     
     
         20 . The method of  claim 17 , wherein the odd carbon fatty acid is dosed at between 1 to 2 gr/kg/day. 
     
     
         21 . The method of  claim 17 , wherein the odd carbon fatty acid comprises 30 to 40 percent of total daily Kcalories. 
     
     
         22 . The method of  claim 17 , wherein the patient's total caloric intake comprises between about 1,200 to 3,000 calories per day. 
     
     
         23 . A method of treating a disease in a mammal resulting from deficiencies of fatty acid oxidaase disease comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising recombinant glycosylated enzymatically active α-glucosidase A or an enzymatically active fragment thereof and a pharmaceutically effective amount of an odd carbon fatty acid. 
     
     
         24 . The method of  claim 23 , wherein the effective amount recombinant glycosylated enzymatically active α-glucosidase A or an enzymatically active fragment needed to treat a mammal is reduced by between about 20 and 80 percent. 
     
     
         25 . The method of  claim 23 , wherein the mammal is selected from humans, dogs, cats, horses, hamsters, rats, mice, sheep, goats and pigs. 
     
     
         26 . The method of  claim 23 , wherein the number of daily doses of pharmaceutical composition is administered daily is reduced in half or less. 
     
     
         27 . The method of  claim 23 , wherein the pharmaceutical composition is administered orally, intravenously, intramuscularly, intranasally, intradermally, intraperitoneally, subcutaneously or as a suppository. 
     
     
         28 . The method of  claim 23 , wherein the α-glucosidase A further comprises a pharmacologically acceptable carrier. 
     
     
         29 . The method of  claim 23 , wherein the amount of odd carbon fatty acid is sufficient to be detectable in serum as free heptanoate. 
     
     
         30 . The method of  claim 23 , wherein the recombinant glycosylated enzymatically active α-glucosidase A or an enzymatically active fragment thereof is provided in a sub-optimal amount. 
     
     
         31 . The method of  claim 23 , wherein the effective amount of the odd carbon fatty acid comprises a nutritionally effective amount. 
     
     
         32 . A method of treating a glycogen storage disease comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising an odd-chain fatty acid or ketone. 
     
     
         33 . The method of  claim 32 , wherein the pharmaceutical composition is administered at a daily oral administration dosage of between about 0.5 to about 2.0 grams, per day, per kilogram of patient weight. 
     
     
         34 . The method of  claim 32 , wherein the pharmaceutical composition is in a form adapted for oral administration. 
     
     
         35 . The method of  claim 32 , wherein the pharmaceutical composition is in powder, tablet, gelatin, gelcap, capsule, soft-gel, chewable or liquid form. 
     
     
         36 . The method of  claim 32 , wherein the patient is a human. 
     
     
         37 . The method of  claim 32 , wherein the therapeutically effective amount comprises between about 20 and 40% of the patient's daily caloric intake. 
     
     
         38 . A method of treating muscle weakness comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising an odd-chain fatty acid or ketone, wherein the patient's muscle weakness is reduced and pulmonary function is increased. 
     
     
         39 . The method of  claim 38 , wherein the muscle weakness is caused by acute muscle usage. 
     
     
         40 . The method of  claim 38 , wherein the muscle weakness is chronic. 
     
     
         41 . A method of treating urgency in urination and defecation comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising an odd-chain fatty acid or ketone. 
     
     
         42 . A method of protein sparing comprising administering to a patient in need of protein sparing with a therapeutically effective amount of a pharmaceutical composition comprising an odd-chain fatty acid or ketone. 
     
     
         43 . The method of  claim 42 , further comprising providing the patient with one or more vitamins, minerals, amino acids, lipids, nucleic acids, co-factors, pro-vitamins, and combinations of mixtures thereof. 
     
     
         44 . The method of  claim 42 , further comprising providing the patient a nutritionally effective amount of branched amino acids. 
     
     
         45 . An immediate release product comprising an at least partially water-soluble ketogenic odd-chain fatty acid in an immediate release form that becomes immediately bioavailable in a subject. 
     
     
         46 . The product of  claim 45 , wherein bioavailability is determined by serum levels of odd-chain fatty acids. 
     
     
         47 . The product of  claim 45 , wherein the product is adapted for parenteral, intravenous, oral, intramuscular, intraaortal, intrahepatic, intragastric, intranasal, intrapulmonary, intraperitoneal, subcutaneous, rectal, vaginal, intraosseal or dermal delivery. 
     
     
         48 . The product of  claim 45 , wherein the product is at least partially dry. 
     
     
         49 . The product of  claim 45 , further comprising one or more vitamins, minerals, amino acids, lipids, nucleic acids, co-factors, pro-vitamins, and combinations of mixtures thereof. 
     
     
         50 . The product of  claim 45 , produced by solution precipitation methods, anti-solvent precipitation, spray drying, spray freezing, evaporative precipitation into an aqueous solution, wet milling, mechanical milling, vacuum-drying, vacuum-heating or lyophilization. 
     
     
         51 . The product of  claim 45 , wherein the compound comprises particles that are amorphous, crystalline or semi-crystalline. 
     
     
         52 . The product of  claim 45 , wherein the product is produced by evaporative precipitation into an aqueous solution and wherein the formulation has a drug-to-excipient ratio greater than about 3:1. 
     
     
         53 . The product of  claim 45 , wherein the product comprises a ketogenic odd-chain fatty acid to-excipient ratio that is greater than about 1:10, 1:1, 5:1, 7:1 or 10:1. 
     
     
         54 . The product of  claim 45 , wherein the product comprises a ketogenic odd-chain fatty acid to-emulsifier ratio is about 1:10, 1:1, 4:1, 7:1, 10:1, 13:1, 15:1, 25:1 or 40:1. 
     
     
         55 . A method of providing nutritional support for surgery comprising providing a patient in need of supplemental metabolic support a nutritionally effective amount of a ketogenic odd-chain fatty acid comprising between about 30-35% of total Kcal/day. 
     
     
         56 . A method for ameliorating the effects of physical exertion, the method comprising the administration to a person in need of such amelioration a composition of  claim 1 . 
     
     
         57 . A composition for post-operative nutritional support comprising a nutritionally effective amount of a compound that provides both 2-carbon and 3-carbon citric acid cycle metabolites. 
     
     
         58 . The composition of  claim 57 , wherein the 2-carbon metabolite is acetyl-CoA and the 3-carbon metabolite is propionyl-CoA. 
     
     
         59 . The composition of  claim 57 , wherein the compound comprises a ketogenic odd-chain fatty acid comprising between about 30-35% of total Kcal/day. 
     
     
         60 . The composition of  claim 57 , further comprising a nutritionally effective amount of one or more essential amino acids. 
     
     
         61 . The composition of  claim 57 , further comprising a nutritionally effective amount of one or more essential saccharides. 
     
     
         62 . A modified release product having two portions, wherein a first portion comprises a first quantity of a ketogenic odd-chain fatty acid in an immediate release form which becomes fully bioavailable in the subject's stomach and a second portion comprises a second compound in a sustained release form wherein the ratio of the first quantity to the second quantity provides a Cmax in a human subject equivalent to the Cmax obtained when the first of one or more doses of a standard immediate release formulation having one third the amount of the ketogenic odd-chain fatty acid is dosed every four hours over a 12 hour period and wherein the product also provides therapeutically effective bioavailability for at least twelve hours after a single dose in a human subject according to serum analysis. 
     
     
         63 . The product of  claim 62 , wherein the second compound comprises a ketogenic odd-chain fatty acid. 
     
     
         64 . The product of  claim 62 , wherein the second compound comprises one or more vitamins, minerals, amino acids, lipids, nucleic acids, co-factors, pro-vitamins, and combinations of mixtures thereof. 
     
     
         65 . The product of  claim 62 , wherein the second compound comprises alanine and glutamine. 
     
     
         66 . A diet comprising:
 a ketogenic odd-chain fatty acid comprising between about 5 to 40% of total Kcal/day; essential fats of between about 5-20% total Kcal/day; carbohydrates restricted to about 20 to 40% total Kcal/day of the diet; and a protein content of between about 15 to 30% total Kcal/day.   
     
     
         67 . The diet of  claim 66 , wherein the essential fats comprise between about 10-15% of the total Kcal/day. 
     
     
         68 . The diet of  claim 66 , wherein the daily carbohydrate intake provides about 30% of the total Kcal/day. 
     
     
         69 . The diet of  claim 66 , wherein the daily protein intake provides about 20% of the total Kcal/day. 
     
     
         70 . The diet of  claim 66 , wherein the ketogenic odd-chain fatty acid comprise between about 1-4 gm/Kg/day. 
     
     
         71 . The diet of  claim 66 , wherein the ketogenic odd-chain fatty acid comprises one or more odd-chain fatty acids selected from C5, C7, C15, and mixtures or combinations thereof. 
     
     
         72 . The diet of  claim 66 , wherein the ketogenic odd-chain fatty acid comprises triheptanoin, a triglyceride, a salt or derivative thereof. 
     
     
         73 . The diet of  claim 66 , wherein the ketogenic odd-chain fatty acid comprises n-heptanoic acid, a triglyceride, or a salt or derivative thereof, or combinations thereof. 
     
     
         74 . A beverage comprising: water, carbohydrates, electrolytes and a ketogenic odd-chain fatty acid in a concentration of between about 0.5% to about 5.0%. 
     
     
         75 . The beverage of  claim 74 , wherein the concentration of the ketogenic odd-chain fatty acid is about 1.0%. 
     
     
         76 . The beverage of  claim 74 , wherein the ketogenic odd-chain fatty acid is emulsified. 
     
     
         77 . The beverage of  claim 74 , wherein the ketogenic odd-chain fatty acid comprises between about 20-30% of the daily caloric intake. 
     
     
         78 . The beverage of  claim 74 , wherein the ketogenic odd-chain fatty acid comprise one or more odd-chain fatty acids selected from C5, C7, C15, and mixtures or combinations thereof. 
     
     
         79 . A beverage comprising the following ingredients: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Ingredient 
                   Approximate Concentration 
                 
                     
                     
                 
                     
                   Potassium 
                    2 meq/l 
                 
                     
                   Sodium 
                   26 meq/l 
                 
                     
                   Glucose 
                   4% 
                 
                     
                   Pyruvate 
                   1% 
                 
                     
                   ketogenic odd-chain fatty acid 
                   1 to 20% 
                 
                     
                   Emulsifier 
                   0.1 to 2.0% 
                 
                     
                   water 
                   balance. 
                 
                     
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         80 . A beverage that provides a source of immediate energy comprising a composition by weight: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Total Carbohydrate 
                    0.4-3.5% 
                 
                     
                   Ketogenic odd-chain fatty acid 
                    0.1 to 20% 
                 
                     
                   Emulsifier 
                   0.1 to 2.0% 
                 
                     
                   Sodium Chloride 
                   0.16-0.33% 
                 
                     
                   Potassium Chloride 
                   0.03-0.13% 
                 
                     
                   Free Citric Acid 
                   0.026-0.26%  
                 
                     
                   Water 
                   balance 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         81 . A dry beverage concentrate for enhanced, immediate energy requirements in a mammalian body comprising a composition by weight in water: an emulsified, ketogenic odd-chain fatty acid 0.1-25%; total carbohydrate of 0.4-3.5%; sodium chloride 0.16-0.22%; potassium chloride 0.03-0.13%; and free citric acid 0.026-0.26%, the concentrate suitable for mixture with water to yield a beverage. 
     
     
         82 . A food composition comprising:
 a mixture of ingredients selected to make one or more snacks, soups, salads, cakes, cookies, crackers, breads, ice creams, yogurts, puddings, custards, baby foods, medicinal foods, sports bars, breakfast cereals and beverages; and   a ketogenic odd-chain fatty acid in a concentration of between about 0.5% to about 5.0% of the composition.   
     
     
         83 . The composition of  claim 82 , wherein the food composition comprises grains, fruits, nuts and supplemental dietary fiber in the form of compressed flakes and combinations thereof. 
     
     
         84 . The composition of  claim 82 , wherein the food composition comprises compressed flakes of supplemental dietary fiber comprise at least one source of supplemental dietary fiber and at least one binder material. 
     
     
         85 . The composition of  claim 82 , wherein the wherein the food composition comprises supplemental a dietary fiber selected from the group consisting of apple fiber, corn bran, soy fiber, pectin, guar gum, gum ghatti, and gum arabic, as well as mixtures thereof. 
     
     
         86 . The composition of  claim 82 , wherein the wherein the food composition comprises a binder material selected from the group consisting of rice flour, wheat flour, oat flour, corn flour, rye flour and potato flour, as well as mixtures thereof. 
     
     
         87 . The composition of  claim 82 , further defined as comprising a pre-cooked edible and chewable product selected from the group consisting of breakfast cereals, snacks, soups, salads, cakes, cookies, crackers, puddings, ice creams, yogurts, puddings, custards, baby foods, medicinal foods, sports bars, and beverages. 
     
     
         88 . The composition of  claim 82 , wherein the composition is extrusion cooked. 
     
     
         89 . An ingredient for fortification of a food product comprising an emulsified ketogenic odd-chain fatty acid in a concentration of between about 0.5% to about 5.0% of the food supplement. 
     
     
         90 . An orally administratable partially dry unit dosage comprising at least about 10 to 1,000 mg of a ketogenic odd-chain fatty acid. 
     
     
         91 . A nutritional supplement comprising:
 a nutritionally effective amount of a ketogenic odd-chain fatty acid that are metabolized into both 2-carbon and 3-carbon citric acid cycle metabolites, and the ketogenic odd-chain fatty acid is selected from the group consisting of a C5, C7, C15, and mixtures or combinations thereof.   
     
     
         92 . A method for increasing the immediately available energy supply to a cell, comprising exposing the cell to an effective dosage of a ketogenic odd-chain fatty acid that represents 20-35% of the cellular requirement of kCals per day. 
     
     
         93 . A method for increasing the immediately available energy supply to a mammal, comprising providing the mammal with an effective dosage of a ketogenic odd-chain fatty acid that comprises 30-35% of the mammal's kCal per day. 
     
     
         94 . The method of  claim 93 , wherein the ketogenic odd-chain fatty acid comprises one or more odd-chain fatty acids selected from C5, C7, C15, and mixtures or combinations thereof. 
     
     
         95 . An animal feed comprising:
 an odd chain fatty acid present in an amount effective to provide nutritive fat to an animal and a solid nutritive source.   
     
     
         96 . The animal feed of  claim 95 , wherein the odd chain fatty acid is present in an amount of at least about 5% to 40% by weight of the feed. 
     
     
         97 . The animal feed of  claim 95 , wherein the solid nutrititive source includes a source selected from the group consisting of soy, oats, sorghum, whole wheat, whole rice, whole corn and whole barley. 
     
     
         98 . The animal feed of  claim 95 , wherein the solid nutritive source includes a nutritive ingredient selected from the group consisting of vitamins and nutritive minerals. 
     
     
         99 . The animal feed of  claim 95 , wherein the solid nutritive source includes a source selected from the group consisting of a nutritive wheat fraction, a nutritive rice fraction, a nutritive corn fraction, and a nutritive barley fraction. 
     
     
         100 . The animal feed of  claim 95 , wherein the feed is adapted for use by one or more of poultry, livestock, farm-raised fish, crabs, shrimp and fresh-water turtles.