Methods and compositions for treating neuropathies

• US 7,776,326 B2
• Filed: 06/03/2005
• Issued: 08/17/2010
• Est. Priority Date: 06/04/2004
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Milbrandt, Jeffrey, Sasaki, Yo, Araki, Toshiyuki
• Primary Examiner(s): Lilling; Herbert J.
• Application Number:
  US11/144,358
• Publication Number:
  US 20060002914A1
• Time in Patent Office: 1,901 Days
• Field of Search: 424/94.5
• US Class Current: 424/94.5
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7084 Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• CPC Class Codes: A61K 38/45 Transferases (2)
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07H 19/20 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C12N 9/1241 : Nucleotidyltransferases (2.7.7)

Abstract

Methods of treating or preventing axonal degradation in neuropathic diseases in mammals are disclosed. The methods can comprise administering to the mammal an effective amount of an agent that acts by increasing sirtuin activity in diseased and/or injured neurons. The methods can also comprise administering to the mammal an effective amount of an agent that acts by increasing NAD activity in diseased and/or injured neurons. Also disclosed are methods of screening agents for treating a neuropathies and recombinant vectors for treating or preventing neuropathies.

Claims

1. A method of treating an axonopathy in a mammal in need thereof, the method comprising administering to the mammal an agent that acts by increasing sirtuin activity in diseased and/or injured neurons and supporting cells in an amount effective to decrease axonal degeneration.

2. A method according to claim 1, wherein the agent acts by increasing SIRT1 activity.

3. A method according to claim 1, wherein the agent is NAD, NADH, an intermediate of a de novo pathway for synthesizing NAD, an intermediate of a NAD salvage pathway, an intermediate of a nicotinamide riboside kinase pathway or a combination thereof.

4. A method according to claim 1, wherein the agent is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.

5. A method according to claim 1, wherein the mammal is a human.

6. A method in accordance with claim 4 wherein the agent is nicotinamide riboside.