Advancing Type 1 Diabetes and Islet Transplantation Research

A Diabetes Research Institute study introduces two small-molecule drugs that target a pivotal immune checkpoint interaction implicated in the rejection of transplanted cells.

Diabetes Lab

Under the leadership of Peter Buchwald, Ph.D., researchers at the Diabetes Research Institute (DRI), have made significant progress in developing potential therapies for type 1 diabetes (T1D) and islet transplantation.

Their study introduces two novel, small-molecule drugs, DRI-C21041 and DRI-C21095, which were designed, synthesized and tested in-house. These molecules target a pivotal immune checkpoint interaction implicated in both the rejection of transplanted cells and the autoimmune attacks that drive T1D progression.

Implications for Type 1 Diabetes and Transplant Recipients

For individuals at risk of developing T1D, the immune system mistakenly destroys insulin-producing pancreatic cells. This study highlights that by inhibiting the CD40–CD40L interaction, a key pathway in immune activation. These molecules could significantly reduce the incidence of T1D.

In preclinical mouse models, one of the drugs decreased the development of diabetes from 80% to 25%, showcasing its potential as a preventive therapy.

Longitudinal images showing a rejected islet
A rejected islet
an islet treated with the small molecule DRI-C21041, which maintained integrity without rejection even after treatment stopped on post-operative day 60 (POD60)
An islet treated with the small molecule DRI-C21041

In the context of transplantation, these molecules represent a promising approach to safeguarding transplanted beta cells, which are vital for restoring insulin production in individuals with T1D. Unlike conventional immunosuppressive therapies, these small molecules reduce immunogenicity and are easily administered, potentially as oral medications instead of injections. This innovation could alleviate the long-term burden of immune-suppressing drugs for transplant recipients.

The Future of Diabetes Research and Patient Care

This encouraging research, supported by the Diabetes Research Institute Foundation, suggests a new path for safer and more effective therapies for individuals with T1D and transplant recipients. These findings open doors for future studies and could ultimately lead to the development of treatments that prevent diabetes and protect transplants long term by inducing operational immune tolerance without the risks associated with current immunosuppressive drugs.


Tags: diabetes, Diabetes Research Institute, Dr. Peter Buchwald, islet cell transplantation, type 1 diabetes