Safe Gene Therapy for Type 1 Diabetes
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2010
- Accession Number
- ADA612978
Entities
People
- Massimo Trucco
Organizations
- University of Pittsburgh