Methods and compositions for treatment of metabolic disorders

• US 9,907,848 B2
• Filed: 09/09/2013
• Issued: 03/06/2018
• Est. Priority Date: 08/03/2010
• Status: Active Grant

• Current Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Original Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Inventors: Exley, Mark A., Lynch, Lydia, O'Shea, Donal, O'Farrelly, Cliona, Balk, Steven P.
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US14/021,825
• Publication Number:
  US 20140079771A1
• Time in Patent Office: 1,639 Days
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7032 attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/4613 Natural-killer cells [NK or NK-T]
• CPC Class Codes: A61K 39/464 characterised by the antigen targeted or presented
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00

Abstract

The present invention relates to the discovery that increases in invariant NKT cell (iNKT) number and/or activity can reduce the incidence or severity of metabolic disorders such as obesity and diabetes. The invention accordingly features methods, kits, and compositions for the treatment of such metabolic disorders by administration of a composition capable of increasing iNKT activity.

Claims

1. A method of treating a human subject suffering from a metabolic disorder, said method comprising administering to said human subject an amount of α

-galactosylceramide that is sufficient to reduce the size of adipocytes of the subject.

2. The method of claim 1, wherein said α

-galactosylceramide is a bacterial α

-galactosylceramide capable of activating invariant (iNKT) cell activity.

3. The method of claim 2, wherein said iNKT is an autologous iNKT.

4. The method of claim 1, wherein said α

-galactosylceramide is administered to said human subject in a composition comprising said α

-galactosylceramide and a pharmaceutically acceptable carrier.

5. The method of claim 4, wherein said composition is administered intravenously, intramuscularly, orally, by inhalation, parenterally, intraperitoneally, intraarterially, transdermally, sublingually, nasally, transbuccally, liposomally, adiposally, ophthalmically, intraocularly, subcutaneously, intrathecally, topically, or locally.

6. The method of claim 1, wherein said metabolic disorder is diabetes, obesity, diabetes as a consequence of obesity, hyperglycemia, dyslipidemia, hypertriglyceridemia, syndrome X, insulin resistance, impaired glucose tolerance (IGT), diabetic dyslipidemia, hyperlipidemia, a cardiovascular disease, or hypertension.

7. The method of claim 6, wherein said diabetes is type I diabetes or type II diabetes.

8. The method of claim 1, wherein said subject is further administered a second therapeutic for treating said metabolic disorder.

9. The method of claim 6, wherein said metabolic disorder is obesity.

10. The method of claim 1, wherein said amount of α

-galactosylceramide increases iNKT cell activity in adipose iNKT cells.