Gene therapy shows promise in stopping the immune attack on insulin-producing cells

JDRF-funded researchers are using gene therapy in a promising approach to stopping the autoimmune attack that triggers type 1 diabetes (T1D). The gene therapy manipulates the body’s varied immune cells, which perform different functions. Some immune cells, called T-effector cells, attack foreign material in the body that may cause disease, whereas others, called T-regulatory cells, keep them in check. In people with T1D, T-effector cells mistakenly attack the body’s insulin-producing beta cells, and T-regulatory cells fail to stop them. The goal of the new gene therapy is to stimulate T-regulatory cells to halt the attack on beta cells.

To do this, Maria Grazia Roncarolo, M.D. (who has recently relocated to Stanford University from the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy), and a team of researchers inserted an insulin gene fragment into the liver of a mouse model of T1D. They targeted the liver because it is known to promote immune regulation. Indeed, this approach stimulated T-regulatory cells in pre-diabetic mice, protecting beta cells from attack. According to a paper published in Science Translational Medicine, the gene insertion helped to preserve beta cells and halted the progression of T1D in mice at very early stages of the disease before symptoms were noticeable. Furthermore, combining the gene insertion with another therapeutic that specifically targeted T-effector cells reduced high blood glucose levels in mice closer to disease onset and reversed disease at later stages in 75 percent of treated mice.

The findings from this JDRF-supported research underscore the importance of targeting T1D gene therapy to an appropriate location in the body. Targeting an organ that promotes immune regulation, such as the liver, may be able to reset or reverse the disease process. This study also highlights the benefit of combining therapies that control T-effector cells with approaches that stimulate T-regulatory cells in order to achieve the desired treatment outcome.

This novel application of gene therapy alone or with additional therapies is representative of several approaches JDRF is taking to prompt the immune system to stop destroying beta cells, replenish the supply of these cells and restore insulin production in people with T1D. While more research is needed to determine whether this strategy can stimulate a similar immune response in people and can be translated into safe and effective therapies for T1D, these initial results are encouraging.