Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders

• US 20070149466A1
• Filed: 03/16/2006
• Published: 06/28/2007
• Est. Priority Date: 07/07/2005
• Status: Abandoned Application

• Current Assignee: Sirtris Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Original Assignee: Sirtris Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Inventors: Milne, Jill, Milburn, Michael, Auwerx, Johan, Dipp, Michelle, Lagouge, Marie, Argmann, Carmen
• Application Number:
  US11/374,295
• Publication Number:
  US 20070149466A1
• Time in Patent Office: Days
• US Class Current: 514/43
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23L 33/30 Dietetic or nutritional methods, e.g. for losing weight A23L33/10 takes precedence
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Provided herein are methods and compositions for treating or preventing metabolic disorders, such as obesity and diabetes. Methods may comprise modulating the activity or level of a sirtuin, such as SIRT1 or Sir2. Exemplary methods comprise contacting a cell with a sirtuin activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin, or an inhibitory compound, such as nicotinamide.

Claims

1-123. -123. (canceled)

124. A pharmaceutical dosage form, comprising a quantity of a sirtuin activating compound having a sirtuin activating effect equal to or greater than 200 mg resveratrol.

125. The pharmaceutical dosage form of claim 124, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.

126. The pharmaceutical dosage form of claim 124, further comprising a lipid-lowering, an anti-obesity or an anti-diabetic agent or a combination thereof.

127. A method of treating obesity, reducing the weight, preventing weight gain, and/or treating an insulin resistance disorder in a subject in need thereof, comprising administering daily to the subject an amount of a sirtuin activating compound that has a sirtuin activating effect equal to or greater than 18 mg/kg resveratrol.

131. The method of any of claims 127-130, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.

132. The method of any of claims 127-130, further comprising administering to the subject a lipid-lowering, an anti-obesity or an anti-diabetic agent or a combination thereof.

128. A method of treating obesity in a subject in need thereof that consumes a high fat diet, comprising administering to the subject an amount of a sirtuin activating compound.

129. A method of treating obesity in a subject in need thereof, comprising administering to the subject an effective amount of a sirtuin activating compound, wherein said subject does not reduce calorie consumption, increase activity or a combination thereof to an extent sufficient to cause weight loss in the absence of a sirtuin activating compound.

130. A method of protecting pancreatic beta cells in a subject in need thereof, comprising administering to the subject an effective amount of a sirtuin activating compound.

133. A food or beverage fit for consumption by a mammal, wherein said food or beverage comprises a supplement of one or more sirtuin activating compounds and wherein (a) the concentration of the one or more sirtuin activating compounds in said food or beverage has a sirtuin activating effect equal to or greater than the sirtuin activating effect of 11 mg/g resveratrol;

(b) said food or beverage does not include grapes, mulberries, blueberries, raspberries, peanut, milk, yeast or an extract thereof;

(c) an 8 fluid ounce serving of the beverage comprising a quantity of a sirtuin activating compound having a sirtuin activating effect equal to or greater than the sirtuin activating effect of 25 mg resveratrol;

(d) a single serving of the food comprises a quantity of a sirtuin activating compound having a sirtuin activating effect equal to or greater than the sirtuin activating effect of 100 mg resveratrol;

or (e) said food or beverage comprises a supplement of one or more stabilized sirtuin activating compounds.

134. The food or beverage of claim 133, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.

135. The food or beverage of claim 133, further comprising one or more lipid lowering, anti-obesity or anti-diabetic agents or a combination thereof.

136. A method for treating a disease or disorder in a subject that would benefit from increased mitochonadrial activity, comprising administering daily to a subject in need thereof an amount of a sirtuin activating compound that has a sirtuin activating effect equal to or greater tan 18 mg/kg resveratrol.

137. The method of claim 136, wherein the sirtuin modulating compound increases mitochondrial activity without increasing mitochondrial mass or wherein the sirtuin modulating compound increases mitochondrial mass.

138. The method of claim 136, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.

139. The method of claim 136, further comprising administering to the subject one or more of the following:

a vitamin, cofactor or antioxidant.

140. The method of claim 136, further comprising administering to the subject one or more agents that alleviate a symptom of the disease or disorder.

141. A method for treating hypothermia, enhancing motor performance or muscle endurance, decreasing fatigue, or increasing recovery from fatigue, comprising administering to a subject a therapeutically effective amount of at least one sirtuin activating compound.

142. The method of claim 141, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.

143. A method for treating or preventing muscle tissue damage associated with hypoxia or ischemia or a condition wherein motor performance or muscle endurance is reduced comprising administering daily to a subject in need thereof an amount of a sirtuin activating compound that has a sirtuin activating effect equal to or greater than 18 mg/kg resveratrol.

144. A method for increasing cellular ATP levels in a subject, comprising administering to the subject a therapeutically effective amount of a sirtuin activating compound.

145. A method for prolonging the lifespan of a subject, treating or preventing a neurodegenerative disorder in a subject, treating or preventing a blood coagulation disorder, treating or preventing an ocular disease or disorder, treating or preventing chemotherapeutic induced neuropathy, treating or preventing neuropathy associated with an ischemic event or disease, treating or preventing a polyglutamine disease or treating or preventing a disease or disorder associated with cell death or aging in a subject, comprising administering daily to a subject in need thereof an amount of a sirtuin activating compound that has a sirtuin activating effect equal to or greater than 18 mg/kg resveratrol.

146. The method of claim 145, wherein the sirtuin activating compound is resveratrol or nicotinamide riboside.