METHODS FOR PREVENTING OR TREATING METABOLIC SYNDROME

• US 20110039766A1
• Filed: 08/11/2010
• Published: 02/17/2011
• Est. Priority Date: 08/12/2009
• Status: Abandoned Application

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Szeto, Hazel H.
• Application Number:
  US12/854,551
• Publication Number:
  US 20110039766A1
• Time in Patent Office: Days
• US Class Current: 514/4.8
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The invention provides methods of preventing or treating metabolic syndrome in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof.

Claims

1. A method of treating or preventing metabolic syndrome in a mammalian subject, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of the peptide D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or Phe-D-Arg-Phe-Lys-NH₂.

2. The method of claim 1, wherein the metabolic syndrome is associated with resistance to insulin-mediated glucose uptake, glucose intolerance, hyperinsulemia, increased LDL-cholesterol, increased VLDL, increased triglycerides, decreased HDL-cholesterol, increased plasminogen activator inhibitor-1 (PAI-1) levels or hypertension.

3. The method of claim 1, wherein the metabolic syndrome is characterized by three or more of the following criteria:

(a) abdominal obesity;

waist circumference >

102 cm in men and >

88 cm in women;

(b) hypertriglyceridemia;

≧

150 mg/dl (1.695 mmol/l);

(c) low HDL cholesterol;

<

40 mg/dl (1.036 mmol/l) in men and <

50 mg/dl (1.295 mmol/l) in women;

(d) high blood pressure;

≧

130/85 mm Hg; and

(e) high fasting glucose;

≧

110 mg/dl (>

6.1 mmol/l).

4. The method of claim 1, wherein the metabolic syndrome is characterized by diabetes, impaired glucose tolerance, impaired fasting glucose, or insulin resistance plus two or more of the following abnormalities:

(a) high blood pressure;

≧

160/90 mm Hg;

(b) hyperlipidemia;

triglyceride concentration ≧

150 mg/dl (1.695 mmol/l) and/or HDL cholesterol <

35 mg/dl (0.9 mmol/l) in men and <

39 mg/dl (1.0 mmol/l) in women;

(c) central obesity;

waist-to-hip ratio of >

0.90 in men or >

0.85 in women or BMI >

30 kg/m²; and

(d) microalbuminuria;

urinary albumin excretion rate ≧

20 μ

g/min or an albumin to creatinine ratio ≧

20 mg/g.

5. The method of claim 1, wherein the metabolic syndrome is characterized by three or more of the following criteria:

(a) triglycerides >

150 mg/dl;

(b) systolic blood pressure (BP)≧

130 mm Hg or diastolic blood pressure ≧

85 mm Hg or on antihypertensive treatment;

(c) high-density lipoprotein cholesterol <

40 mg/dl;

(d) fasting blood sugar (FBS)>

110 mg/dl; and

(e) body mass index >

28.8 kg/m².

6. The method of claim 1, wherein the metabolic syndrome is treated through improvement of lipid metabolism compared to the subject'"'"'s lipid metabolism before being administered the peptide.

7. The method of claim 6, wherein the improvement in lipid metabolism is reduction of blood triglyceride level compared to the subject'"'"'s blood triglyceride level before being administered the peptide.

8. The method of claim 6, wherein the improvement in lipid metabolism is improvement of blood HDL/LDL cholesterol ratio compared to the subject'"'"'s blood HDL/LDL cholesterol before being administered the peptide.

9. The method of claim 1, wherein the metabolic syndrome is treated by reducing blood sugar level compared to the subject'"'"'s blood sugar level before being administered the peptide.

10. The method of claim 1, wherein the metabolic syndrome is treated by a reduction in body weight compared to the subject'"'"'s body weight before being administered the peptide.

11. The method of claim 1, wherein the subject is a human.

12. The method of claim 1, wherein the peptide is administered prior to the onset of type II diabetes.

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

14. The method of claim 1 further comprising the step of identifying the mammal in need of treating or preventing metabolic syndrome.

15. The method of claim 1 further comprising the step of monitoring the mammal for treatment or prevention of metabolic syndrome.