METHODS FOR TREATING CACHEXIA AND LYMPHOPENIA

• US 20100080784A1
• Filed: 09/10/2009
• Published: 04/01/2010
• Est. Priority Date: 09/12/2008
• Status: Abandoned Application

• Current Assignee: Torrey Pines Institute for Molecular Studies
• Original Assignee: Torrey Pines Institute for Molecular Studies
• Inventors: Davies, Joanna
• Application Number:
  US12/557,373
• Publication Number:
  US 20100080784A1
• Time in Patent Office: Days
• US Class Current: 424/93.710
• 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: G01N 2333/70514 CD4
• CPC Class Codes: G01N 2333/70585 CD44
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/56972 White blood cells

Abstract

Disappearance of a cell population, designated CD4⁺ CD44^v.low, has been shown to be associated with cachexia and lymphopenia, and those conditions can be treated or delayed by administering those cells to a patient. In addition, disclosed are assays for those cells for diagnosing or prognosticating cachexia and/or lymphopenia and the end of the honeymoon period in Type I diabetes. Furthermore, disclosed herein are methods related to the use of CD4+ CD44v.low cells in promoting insulin-secreting beta cell mass.

Claims

1. A method of treating, ameliorating, preventing, or delaying the onset of cachexia in a patient comprising:

administering isolated or purified CD4+ T cells to the patient.

2. The method of claim 1, further comprising:

obtaining a cell sample from a mammal;

isolating or purifiying CD4+ T cells from the cell sample; and

expanding the isolated or purified T cells.

3. The method of claim 1, wherein the isolated or purified CD4+ T cells are CD4+ CD44^v.low

4. The method of claim 2, wherein the cell sample comprises a blood sample.

5. The method of claim 2, wherein the cell sample comprises a tissue sample.

6. The method of claim 2, wherein the cell sample comprises lymph tissue.

7. The method of claim 2, wherein the mammal is the patient.

8. The method of claim 2, wherein the mammal is not the patient.

9. The method of claim 1, wherein the cachexia is associated with a disease selected from the group consisting of diabetes mellitus, cancer, AIDS, aging, an autoimmune disorder, chronic viral infection, chronic bacterial infection, chronic fungal infection, and end-stage organ failure.

10. The method of claim 9, wherein the disease is diabetes mellitus.

11. The method of claim 10, wherein the diabetes mellitus is Type I diabetes.

12. The method of claim 1, wherein the isolated T cells are isolated using antibodies.

13. The method of claim 12, wherein the antibodies are at least one of anti-CD4 and anti-CD44.

14. The method of claim 1, wherein the isolated T cells are expanded with growth factors.

15. The method of claim 1, wherein the T cells are administered to the patient by one or more of the routes consisting of intravenous, intraperitoneal, intramuscular, subcutaneous, nasal and oral.

16. The method of claim 1, wherein the T cells are administered to the patient by an intramuscular route.

17. The method of claim 1, wherein the patient is human.

18. The method of claim 17, wherein the T cells administered to the human patient comprise between about 10⁸ and about 10¹¹ cells.

19. An isolated T cell population, comprising an isolated population of T cells characterized as CD4+ CD44^v.low.

20. The isolated T cell population of claim 19, further in combination with an aqueous vehicle and an additional pharmaceutically acceptable excipient.

21. A method of inhibiting or reversing lymphopenia in a patient comprising:

administering isolated or purified CD4+ T cells to the patient.

22. The method of claim 21, further comprising:

obtaining a cell sample from a mammal;

isolating or purifying CD4+ T cells from the cell sample; and

expanding the isolated or purified T cells.

23. The method of claim 22, wherein the isolated or purified CD4+ T cells are CD4+ CD44^v.low.

24. The method of claim 22, further comprising providing to said patient a therapy.

25. A method of treating, ameliorating or preventing diabetes in a patient comprising:

administering isolated CD4+ T cells to the patient.

26. The method of claim 25, further comprising:

obtaining a cell sample from a mammal;

isolating CD4+ T cells from the cell sample; and

expanding the isolated T cells.

27. The method of claim 25, wherein the isolated CD4+ T cells are CD4+ CD44^v.low.

28. A method for diagnosing cachexia in a patient, comprising:

identifying a patient at risk for cachexia;

determining a level of CD4+ CD44^v.low T cells in a biological sample from said patient; and

assessing whether the amount of CD4+ CD44^v.low T cells is at a level which is lower than a predetermined level.

29. A method for diagnosing the onset of a honeymoon period in a patient suffering from Type 1 diabetes, comprising:

identifying a patient with Type 1 diabetes prior to said honeymoon period;

determining a level of CD4+ CD44^v.low T cells in a biological sample from said patient; and

assessing whether the amount of CD4+ CD44^v.low T cells is at a level which is higher than a predetermined level.

30. A method for diagnosing the loss of a honeymoon period in a patient suffering from Type 1 diabetes, comprising:

identifying a patient with Type 1 diabetes within said honeymoon period;

determining a level of CD4+ CD44^v.low T cells in a biological sample from said patient; and

assessing whether the amount of CD4+ CD44^v.low T cells is at a level which is lower than a predetermined level.

31. A method for monitoring the progress of a cachexia therapy in a patient comprising:

identifying a patient with cachexia;

providing said subject a cachexia therapy;

determining a level of CD4+ CD44^v.low T cells in a biological sample in said patient, before a treatment with said cachexia therapy and during or after a period of said treatment.

32. A method for determining the response to a cachexia therapy in a patient comprising:

identifying a patient with a cachexia;

providing said patient a cachexia therapy; and

determining a level of CD4+ CD44^v.low T cells in a biological sample in said patient, before a treatment with said cachexia therapy and during or after a period of said treatment.

33. A method for promoting the responsiveness to a therapy for a disorder:

identifying a patient with the disorder;

administering isolated or purified CD4+ T cells to the patient;

34. The method of claim 33, further comprising:

obtaining a cell sample from a mammal;

isolating or purifiying CD4+ T cells from the cell sample; and

expanding the isolated or purified T cells.

35. The method of claim 33, wherein the isolated or purified CD4+ T cells are CD4+ CD44^v.low.

36. The method of claim 35, further comprising providing to said patient said therapy for said disorder.

37. The method of claim 33, wherein said disorder is cachexia.

38. The method of claim 33, wherein said disorder is Type I diabetes.

39. A method of identifying a patient likely to be responsive to a therapy for a disorder comprising:

identifying a patient with said disorder;

determining a level of CD4+ CD44^v.low T cells in a biological sample from said patient; and

assessing whether the amount of CD4+ CD44^v.low T cells is at a level which is greater than a predetermined level.

40. The method of claim 39, wherein said disorder is cachexia.

41. The method of claim 39, wherein said disorder is Type 1 diabetes.

42. A method for promoting the onset of the honeymoon period in Type 1 diabetes, comprising:

administering isolated or purified CD4+ T cells to the patient.

43. The method of claim 42, further comprising:

obtaining a cell sample from a mammal;

isolating or purifiying CD4+ T cells from the cell sample; and

expanding the isolated or purified T cells.

44. The method of claim 42, wherein the isolated or purified CD4+ T cells are CD4+ CD44^v.low.

45. A method for delaying the loss of the honeymoon period in Type 1 diabetes, comprising:

administering isolated or purified CD4+ T cells to the patient.

46. The method of claim 45, further comprising:

obtaining a cell sample from a mammal;

isolating or purifiying CD4+ T cells from the cell sample; and

expanding the isolated or purified T cells.

47. The method of claim 45, wherein the isolated or purified CD4+ T cells are CD4+ CD44^v.low.

48. A method of treating, ameliorating or preventing diabetes in a patient comprising:

isolating or purifying pancreatic islets from said patient or other donor;

growing said islets in culture in the presence of CD4+ T cells;

and transplanting said islets into said patient.

49. The method of claim 48, wherein the CD4+ T cells are CD4+ CD44^v.low cells.