Treatment for diabetes

• US 20020081285A1
• Filed: 12/20/2001
• Published: 06/27/2002
• Est. Priority Date: 12/14/1992
• Status: Abandoned Application

• Current Assignee: Anne Lane, Indu Parikh, Ronald V Nardi, Stephen J. Brand
• Original Assignee: Anne Lane, Indu Parikh, Ronald V Nardi, Stephen J. Brand
• Inventors: Nardi, Ronald V., Parikh, Indu, Brand, Stephen J., Lane, Anne
• Application Number:
  US10/029,551
• Publication Number:
  US 20020081285A1
• Time in Patent Office: Days
• US Class Current: 424/93.21
• 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 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]
• CPC Class Codes: C07K 14/595 Gastrins; Cholecystokinins [CCK]

Abstract

Methods and compositions for treating diabetes mellitus in a patient in need thereof are provided. The methods include administering to a patient a composition providing a gastrin/CCK receptor ligand, e.g., a gastrin, and/or an epidermal growth factor (EGF) receptor ligand, e.g., TGF-α, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g., a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g., a TGF-α gene. The methods also include transplanting into a patient cultured pancreatic islets in which mature insulin-secreting beta cells are proliferated by exposure to a gastrin/CCK receptor ligand and an EGF receptor ligand.

Claims

1. A method for treating diabetes mellitus in an individual in need thereof, said method comprising:

administering to said individual a composition providing at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells.

2. The method according to claim 1, wherein said at least one receptor ligand is an EGF receptor ligand selected from the group consisting of EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener.

3. The method according to claim 2, wherein said EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener is human EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 or its congener.

4. A method for providing a patient with diabetes in need thereof with a population of mature insulin-secreting beta cells, said method comprising:

transplanting into said patient cultured pancreatic islets which have been provided with a sufficient amount of at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an epidermal growth factor receptor ligand to induce proliferation of mature insulin-secreting beta cells of said islets prior to said transplanting.

5. The method according to claim 4, wherein said diabetes is Type 2 diabetes.

6. The method according to claim 4, wherein said gastrin/CCK receptor ligand is a gastrin.

7. The method according to claim 4, wherein said epidermal growth receptor ligand is TGF-α

or an EGF selected from the group consisting of EGF1-53, EGF1-48, or its EGF1-47 or EGF1-49 congener.

8. A method for expanding a population of pancreatic beta cells, said method comprising:

providing said pancreatic beta cells with a sufficient amount of a gastrin/CCK receptor ligand and an epidermal growth factor receptor ligand to induce proliferation of said pancreatic beta cells, whereby an expanded population of pancreatic beta cells is obtained.

9. A composition comprising:

pancreatic β

cells, wherein said culture is obtained by providing pancreatic islets with a sufficient amount of a gastrin receptor agonist and an epidermal growth factor receptor agonist to induce proliferation of said pancreatic β

cells.

10. A method for treating diabetes in an individual in need thereof, said method comprising:

administering to said individual a composition comprising at least one receptor ligand selected from the group consisting of a proteinaceous gastrin/CCK receptor ligand and a proteinaceous EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells, wherein said composition is administered systemically.

11. The method according to claim 10, wherein said proteinaceous gastrin/CCK receptor ligand is a gastrin.

12. The method according to claim 10, wherein said proteinaceous EGF receptor ligand is a TGF-α

.

13. The method according to claim 10, wherein said diabetes is type 2 diabetes.

15. The method according to claim 14, wherein said individual.

16. The method according to claim 14, wherein both said gastrin/CCK receptor ligand and said EGF receptor ligand are administered.

17. The method according to claim 16, wherein at least one of said gastrin/CCK receptor ligand and said EGF receptor ligand is a proteinaceous receptor ligand.

14. A method for stimulating pancreatic islet cell neogenesis in an individual in need thereof, said method comprising:

administering to said individual a composition comprising at least one receptor ligand selected from the group consisting of a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting islet cells, wherein said composition is administered systemically.

18. A method for treating diabetes mellitus in an individual in need thereof which comprises administering to the individual a composition providing a gastrin/CCK receptor ligand and an EGF receptor ligand in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells.