Accession Number:

ADA612978

Title:

Safe Gene Therapy for Type 1 Diabetes

Descriptive Note:

Annual rept. 28 Sep 2009-27 Sep 2010

Corporate Author:

PITTSBURGH UNIV PA

Personal Author(s):

Report Date:

2010-10-01

Pagination or Media Count:

39.0

Abstract:

In light of accumulating evidence that the endocrine pancreas has regenerative properties, that hematopoietic chimerism can abrogate destruction of beta cells in autoimmune diabetes, and that in this way physiologically-sufficient endogenous insulin production can be restored in clinically-diabetic NOD mice, recapitulating what has also been sporadically seen in humans, we originally proposed to test reliable and clinically translatable alternatives able to re-establish euglycemia in diabetic patients. Instead of relying on the risky allogeneic BM transplantation to obliterate the autoimmune process that causes type 1 diabetes, we originally proposed to reconstitute, by gene supplantation, susceptible non-Asp57 NOD mice with their own BM genetically engineered ex vivo to also express a resistance Asp57 MHC class II molecule. The thymus of the reconstituted mice -- carrying BM-derived cells that co-expressed both their own diabetogenic non-Asp57 and the transfected Asp57 beta chain -- repopulated by the engineered BM cells, can restore an efficient negative selection and consequently the ability to delete T cells potentially auto-reactive to pancreatic beta cells. These diabetics will then be disease-free.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE