Insulin independence among patients with diabetes utilizing a PPI in combination with an immune tolerance agent

• US 8,808,689 B1
• Filed: 02/15/2013
• Issued: 08/19/2014
• Est. Priority Date: 09/27/2012
• Status: Active Grant

• Current Assignee: Claresa Levetan
• Original Assignee: Perle Bioscience, Inc.
• Inventors: Levetan, Claresa
• Primary Examiner(s): Carlson, Karen Cochrane
• Assistant Examiner(s): MOSS, NATALIE M
• Application Number:
  US13/768,472
• Publication Number:
  US 20140234264A1
• Time in Patent Office: 550 Days
• Field of Search: 424/93.7, 435/325
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

To date, no immune tolerance agent or combination of immune tolerance agents has been able to sustain insulin-independence among type 1 diabetes patients. This patent provides methods and pharmaceutical compositions for providing insulin independence among newly diagnosed and existing type 1 diabetes. Methods include utilization of PPIs, which increase gastrin resulting in the transformation of human ductal tissue into insulin-secreting new beta cells, used in combination with an immune tolerance agent to protect the new insulin-producing beta cells generated by the PPI from immune destruction. Compositions and methods are provided for beta cell generation therapy comprising at least one member from a group of PPIs with formulations selected from immune tolerance agents, when used in combination result in insulin-independence among new and existing type 1 patients whom currently require insulin to sustain life. Compositions and methods are provided for insulin-independence among type 2 patients using PPIs when combined with therapeutic agents utilized for the treatment of type 2 diabetes.

Claims

1. A method of treating a condition that is associated with impaired glucose homeostasis in a subject, the method comprising:

culturing pancreatic extra-islet ductal tissue ex vivo;

contacting the pancreatic extra-islet ductal tissue with a proton pump inhibitor, wherein the amount of proton pump inhibitor is effective for forming beta cells from the pancreatic extra-islet ductal tissue in culture; and

administering the beta cells to the subject.

2. The method of claim 1, further comprising contacting the pancreatic extra-islet ductal tissue with an additional beta regeneration agent, wherein the amount of the additional beta regeneration agent is effective for forming beta cells.

3. The method of claim 2, wherein the additional beta regeneration agent is a Reg Peptide, or a formulation or peptidomimetic of a Reg Peptide.

4. The method of claim 1, wherein the beta cells are administered to the subject through an oral, intravenous, subcutaneous, or intra-arterial route of administration.

5. The method of claim 1, wherein the beta cells are delivered through the umbilical vein, portal vein, or hepatic artery.

6. The method of claim 1, wherein the beta cells are delivered directly to the pancreas or the liver.

7. The method of claim 1, wherein the condition that is associated with impaired glucose homeostasis is new and existing type 1 and 2 diabetes, prediabetes, beta cell deficiency, insulin resistance or impaired glucose metabolism.

8. The method of claim 1, wherein the condition that is associated with impaired glucose homeostasis is associated with autoimmunity and an immune tolerance agent is administered before and/or in parallel with the administration of the beta cells.

9. The method of claim 8, wherein the condition that is associated with impaired glucose homeostasis is type 1 diabetes or LADA.

10. The method of claim 8, wherein the immune tolerance agent is selected from Cyclosporine, hOKT3γ

1, ChAglyCD3, Rapamycin, Tacrolimus, Etanercept, Alefacept, Belatacept, Diapep277, a tuberculosis vaccine, Glutamic Acid Decarboxylase 65 (GAD65) vaccine;

Bacillus Calmette-Gué

rin Vaccine, Mycophenolate Mofetil alone or in combination with Daclizumab;

Rituximab;

Campath-1H, lysofylline;

antithymocyte globulin, Proleukin and the combination of Proleukin and Rapamune, Vitamin D, IBC-VSO vaccine, Ex vivo Expanded Human Autologous CD4+CD127lo/−

CD25+ Polyclonal Regulatory T Cells;

interferon-alpha;

a vaccine using CD4⁺CD25⁺ antigen-specific regulatory T cells, Interleukin-1 Receptor Antagonist (anakinra), and Alpha 1-Antitrypsin.

11. The method of claim 8, wherein the immune tolerance agent is Cyclosporine.

12. The method of claim 1, further comprising administration of a PPI or at least one other beta regeneration agent or both to the subject to stimulate formation of new beta cells in the subject in vivo.

13. The method of claim 12, where the condition that is associated with impaired glucose homeostasis is prediabetes or new onset or pre-existing type 2 diabetes.

14. The method of claim 13, wherein the subject is diabetes drug naï

ve.