Methods for reducing CD36 expression

• US 8,603,971 B2
• Filed: 08/04/2010
• Issued: 12/10/2013
• Est. Priority Date: 09/16/2005
• Status: Active Grant

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Szeto, Hazel H., Liu, Shaoyi, Cho, Sunghee
• Primary Examiner(s): Bradley, Christina
• Application Number:
  US12/850,079
• Publication Number:
  US 20100317571A1
• Time in Patent Office: 1,224 Days
• Field of Search: None
• US Class Current: 514/6.9
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/03 Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 27/02 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular 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: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 5/1008 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/101 : the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/1016 : and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1019 : with the first amino acid being basic
• CPC Class Codes: C07K 5/1024 : with the first amino acid being heterocyclic

Abstract

The invention provides a method for treating one or more complications of diabetes in a mammal. The method comprises administering to a mammal in need thereof an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p_m) and the total number of amino acid residues (r) wherein 3 p_m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p_t) wherein 2a is the largest number that is less than or equal to p_t+1, except that when a is 1, p_t may also be 1.

Claims

1. A method for treating a complication of diabetes in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an aromatic-cationic peptide having the formula D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or Phe-D-Arg-Phe-Lys-NH₂, wherein the complication of diabetes is diabetic nephropathy.

2. The method of claim 1, wherein the peptide has the formula D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂.

3. The method of claim 1, wherein the peptide has the formula Phe-D-Arg-Phe-Lys-NH₂.

4. The method of claim 1, wherein the mammal is a human.

5. The method of claim 1, wherein the mammal is suffering from type II diabetes.

6. The method of claim 1, wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, or intramuscularly.

7. The method of claim 1, wherein the mammal is suffering from type I diabetes.

8. The method of claim 1, wherein the method further treats diabetic apoptosis.

9. The method of claim 8, wherein the diabetic apoptosis is associated with diabetic nephropathy.

10. The method of claim 8, wherein the diabetic apoptosis comprises tubular epithelial cell apoptosis.

11. The method of claim 8, wherein the diabetic apoptosis comprises the loss of proximal tubule brush border.

12. The method of claim 8, wherein the diabetic apoptosis is associated with interstitial fibrosis.

13. The method of claim 8, wherein the diabetic apoptosis is associated with elevated CD36 expression.