TREATMENT OF MITOCHONDRIAL DISORDERS USING A FARNESYL TRANSFERASE INHIBITOR

• US 20100331363A1
• Filed: 04/30/2010
• Published: 12/30/2010
• Est. Priority Date: 11/13/2008
• Status: Abandoned Application

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Link Medicine Corp. (Astrazeneca PLC)
• Inventors: Liu, Zhihua, Lansbury, Peter T. JR., Justman, Craig J., Lynch, Berkley A., Grammatopoulos, Tom N.
• Application Number:
  US12/771,221
• Publication Number:
  US 20100331363A1
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject an amount of a farnesyl transferase inhibitor, wherein the amount administered is sufficient to cause an improvement in mitochondrial health in said subject. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

Claims

2-1. The method of claim 1, wherein administration of said compound increases autophagic flux in said subject, which thereby improves mitochondrial health.

17. A pharmaceutical composition for treating a proteinopathic subject, comprising a compound selected from

18. The pharmaceutical composition according to claim 17 comprising approximately 0.1 mg per day to approximately 50 mg per day of the compound or pharmaceutically acceptable salt thereof.

19. The pharmaceutical composition according to claim 17, wherein the pharmaceutically acceptable salt is the D-tartrate salt of

20. The pharmaceutical composition according to claim 17, wherein the proteinopathic subject is suffering from a neurodegenerative disease, a cognitive impairment, a lysosomal storage disease, an ocular disease, an inflammatory disease, a cardiovascular disease, and a proliferative disease.