Researchers at Northwestern University developed a nanoparticle delivery system for a common immunosuppressant drug that increases the potential of pancreatic islet transplantation as a viable long-term treatment for Type I diabetes. The technology targets the drug to act on the antigen presenting cells of the immune system, rather than T cells. This results in a more selective immunosuppression with fewer side-effects and better long-term viability for transplanted islets, which are typically attacked and destroyed by the immune system. The researchers hope that the technology could pave the way for islet transplantation as a viable treatment, but also enhance the potential to transplant other tissues and organs.

At present, Type I diabetes requires regular measurements of blood glucose and insulin injections. Even with more advanced techniques, such as insulin pumps, there is still a lifelong burden on such patients. Pancreatic islet transplantation could change that by providing long-term control of blood glucose levels, but the technique is still hampered by immune rejection of the transplanted tissue.

Common immunosuppressants, such as rapamycin, don’t currently work to protect the islets adequately, at least at safe doses. The side-effects of such drugs can be difficult to live with, including reduced immune protection against infections such as COVID-19. “To avoid the broad effects of rapamycin during treatment, the drug is typically given at low dosages and via specific routes of administration, mainly orally,” said Evan Scott, a researcher involved in the study. “But in the case of a transplant, you have to give enough rapamycin to systemically suppress T cells, which can have significant side effects like hair loss, mouth sores and an overall weakened immune system.”

To address this, the Northwestern University researchers used nanoparticles to specifically target rapamycin to antigen presenting cells of the immune system, rather than the T cells it usually affects. This results in a more controlled immunosuppression that appears to balance protection for transplanted pancreatic islets with a reasonable safety profile.   

“We wondered, can rapamycin be re-engineered to avoid non-specific suppression of T cells and instead stimulate a tolerogenic pathway by delivering the drug to different types of immune cells?” said Scott. “By changing the cell types that are targeted, we actually changed the way that immunosuppression was achieved.”

So far, the researchers tested the technique in diabetic mice that had received a pancreatic islet transplant. Strikingly, the mice demonstrated minimal side-effects, but suffered no diabetes during the 100 day experiment, suggesting the treatment worked to protect the islets.

Study in Nature Nanotechnology: Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability

Via: Northwestern University