Monoglyceride of Acetoacetate and Derivatives for the Treatment of Neurological Disorders

• US 20110178032A1
• Filed: 07/02/2009
• Published: 07/21/2011
• Est. Priority Date: 07/03/2008
• Status: Active Grant

• Current Assignee: Cerecin, Inc.
• Original Assignee: Accela Incorporated (Piksel Incorporated)
• Inventors: Henderson, Samuel T.
• Granted Patent: US 9,125,881 B2
• Time in Patent Office: Days
• US Class Current: 514/23
• CPC Class Codes: A23L 2/52 Adding ingredients adding preservatives A23L2/44
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00

Abstract

This invention relates to methods of using the monoglyceride of acetoacetate and metabolic precursors for the treatment, prevention, inhibition or alleviation of neurological diseases associated with neuronal hypometabolism, such as Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Friedreich'"'"'s Ataxia (FRDA), GLUT1-deficient Epilepsy, Leprechaunism and Rabson-Mendenhall Syndrome, Coronary Arterial Bypass Graft (CABG) dementia, anesthesia induced memory loss, age associated memory impairment (AAMI), Traumatic Brain Injury (TBI), Huntington'"'"'s disease and many others.

Claims

1. A method of treatment of a disease associated with hypometabolism, which comprises administering to a subject suffering from a disease associated with hypometabolism a composition comprising an effective amount of a compound of formula I:

2. The method of claim 1, wherein the elevated level of ketone bodies are present in the patient'"'"'s blood in a normal range of a physiologic ratio of D-β

-hydroxybutyrate and acetoacetate.

3. The method of claim 1, wherein the disease associated with hypometabolism is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Friedreich'"'"'s Ataxia, GLUT1-deficient Epilepsy, Leprechaunism and Rabson-Mendenhall Syndrome, Coronary Arterial Bypass Graft dementia, anesthesia induced memory loss, age associated memory impairment, or Huntington'"'"'s disease.

4. The method of claim 1 where a compound of formula I are administered at a dose in the range of 0.1 g/kg/day to 10 g/kg/day.

5. The method of claim 1 wherein the patient'"'"'s blood level of ketone bodies is elevated to from 0.2 mM to 20 mM at about two hours post administration.

6. The method of claim 1, wherein Formula I is monoacetoacetin.

7. The method of claim 1, comprising the further step of determining the ApoE status of the mammal and selecting a mammal for treatment if the mammal is ApoE4(−

).

8. The method of claim 1, wherein a second composition is administered, wherein said composition comprises a carbohydrate source.

9. The method of claim 8, wherein the carbohydrate source is glucose.

10. The method of claim 1, wherein the composition further comprises a carbohydrate source.

11. The method of claim 10, wherein the carbohydrate source is glucose.