METHODS FOR TREATING INFLAMMATORY DISORDERS

• US 20090111812A1
• Filed: 06/13/2005
• Published: 04/30/2009
• Est. Priority Date: 06/14/2004
• Status: Abandoned Application

• Current Assignee: MUSC Foundation For Research Development (State of South Carolina)
• Original Assignee: MUSC Foundation For Research Development (State of South Carolina)
• Inventors: Singh, Inderjit, Singh, Avtar
• Application Number:
  US11/570,635
• Publication Number:
  US 20090111812A1
• Time in Patent Office: Days
• US Class Current: 514/237.800
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention relates generally to the fields of molecular biology. More particularly, it concerns materials and methods for the treatment of nitric oxide and cytokind mediated disorders. In a preferred embodiment, PDMP may be used to inhibit the expression of iNOS and pro-inflammatory cytokines such as TNFα and IL1β.

Claims

1. A method of treating type I diabetes in a subject, comprising administering a biologically effective amount of a glycosphingolipid inhibitor to the subject in need of such treatment.

2. The method of claim 1, wherein the glycosphingolipid inhibitor is an inhibitor of glucosylceramide synthase.

3. The method of claim 1, wherein the glycosphingolipid inhibitor is an inhibitor of GalT-2.

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

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

6. The method of claim 4, wherein the biologically effective amount is administered to said mammal.

15. The method of claim 1, wherein the glycosphingolipid inhibitor is a PDMP derivative.

16. The method of claim 15, wherein the PDMP derivative is D-threo-3′

,4′

-ethylenedioxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol or D-threo-4′

-hydroxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol.

17. The method of claim 1, wherein the glycosphingolipid inhibitor is N-butyldeoxynojirimycin.

18. The method of claim 1, wherein the glycosphingolipid inhibitor is Miglustat.

19. The method of claim 1, wherein the glycosphingolipid inhibitor is an inhibitor of sphingosine kinase or sphingosine-1-phosphate phosphatase.

20. The method of claim 1, wherein the glycosphingolipid inhibitor is PDMP.

21. The method of claim 20, wherein the PDMP is in a pharmaceutically acceptable excipient.

22. The method of claim 21, wherein the PDMP is administered with a second pharmaceutical preparation.

23. The method of claim 22, wherein the second pharmaceutical preparation enhances intracellular cAMP.

24. The method of claim 23, wherein the second pharmaceutical preparation is Rolipram.

25. The method of claim 22, wherein the second pharmaceutical preparation comprises GM1.

26. The method of claim 22, wherein the second pharmaceutical preparation comprises an inhibitor of mevalonate synthesis, an inhibitor of the farnesylation of Ras, an antioxidant, an enhancer of intracellular cAMP, an enhancer of protein kinase A (PKA), an inhibitor of NF-κ

.beta. activation, an inhibitor of Ras/Raf/MAP kinase pathway, an inhibitor of mevalonate pyrophosphate decarboxylase or an inhibitor of farnesyl pyrophosphate.

7-14. -14. (canceled)

27-43. -43. (canceled)