Regeneration of islet beta cells by hsp60 derived peptides

A technology for deriving peptides and β cells, which can be applied in the fields of peptide/protein components, medical preparations containing active ingredients, oil/fat/wax non-active ingredients, etc., and can solve the problems of unmet needs of β-cell regeneration.

Inactive Publication Date: 2014-12-10
YEDA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] There is an unmet need to provide effective compositions for the treatment of long established T1D and trigger the regeneration of beta cells

Method used

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  • Regeneration of islet beta cells by hsp60 derived peptides
  • Regeneration of islet beta cells by hsp60 derived peptides
  • Regeneration of islet beta cells by hsp60 derived peptides

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0188] Example 1: Non-obese diabetic NOD mouse model

[0189] Female non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes mimicking human T1D, were used to test the ability of Hsp60 peptides and peptide analogs to induce pancreatic β-cell regeneration. The NOD model has been described, eg, by Elias and Cohen (Lancet 1994, 343, 704-706). Insulitis develops at approximately 4 weeks of age in female NOD mice raised under specific pathogen-free (SPF) conditions. Hyperglycemia started around 12-15 weeks and by 20-30 weeks almost all female NOD mice were severely diabetic and most died without insulin treatment. A modified NOD model was used here, in which treatment was initiated at an advanced stage of the disease, after the mice had lost most of their remaining beta cells. Furthermore, the actual emergence of new beta-cells detected by increased C-peptide levels was measured in the modified protocol, rather than merely preserving initial C-peptide level...

Embodiment 2

[0203] Example 2: Animal Model of Beta Cell Regeneration in Chemically Induced Diabetes

[0204] The ability of DiaPep277 to induce or enhance β-cell regeneration was assessed in animal models in which diabetes was induced chemically rather than by autoimmune response (S. Lenzen, Diabetologia, 2008, 51:216-226).

[0205] In the high-dose streptozotocin model (Arora et al., Global Journal of Pharmacology, 2009, 3:81-84), an IP injection of streptozotocin at a dose of 180 mg / kg chemically destroys β-cells and induces insulin dependent diabetes. This diabetes is not based on autoimmune T cell effectors acting on β cells, but is due to direct chemical toxicity. This high-dose streptozotocin model is essentially different from the repeated low-dose model (40 mg / kg X 5, described in Lukic et al., Developmental Immunology, 1998, Vol.6, pp.119-128) that induces autoimmune disease ).

[0206] Furthermore, an alloxan-induced diabetic mouse model was used in which chemical diabetes wa...

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Abstract

The present invention provides compositions for use in the treatment of long- established type 1 diabetes (TID) using peptides and analogs of heat shock protein 60 (Hsp60). The invention is exemplified using DiaPep277, a peptide analog of human Hsp60, which is shown to induce increase in plasma C-peptide and regeneration of islet beta cells. The invention further relates to regimens useful for treatment of long established TID in patients having no demonstrable islet beta cell-function.

Description

field of invention [0001] The present invention relates to methods of regenerating pancreatic beta cells and treating type 1 diabetes (T1D) in patients with long term disease and no residual beta cell function. The method involves administering a peptide derived from heat shock protein 60 (Hsp60), or an analog thereof such as DiaPep277. Background of the invention [0002] Type 1 diabetes (T1D, also known as insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease that results in the destruction of beta cells in the pancreas. The breakdown of glucose homeostasis and the clinical manifestations of the disease are thought to occur only after 80-90% of the pancreatic beta cells are inactivated by the immune response. Early diabetes can be diagnosed only after the onset of the autoimmune process by detection of immune markers of β-cell autoimmunity. [0003] C-peptide is a protein fragment produced by β-cell cleavage pre-insulin during endogenous insulin biosynthesi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K38/17A61K9/00
CPCA61K9/0019A61K9/0024A61K38/164A61K47/44A61K38/1709
Inventor 艾润·R·科恩拉阿南·马加利特
Owner YEDA RES & DEV CO LTD
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