Researchers at Northwestern University have developed a nanoparticle delivery system for a common immunosuppressive drug that increases the potential for pancreatic islet transplantation as a viable long-term treatment for type I diabetes. act on antigen-presenting immune system cells, rather than T cells. This results in more selective immunosuppression with fewer side effects and better long-term viability for transplanted islets, which normally they are attacked and destroyed by the immune system. Researchers hope the technology could pave the way for islet transplantation as a viable treatment, but also improve the potential for transplanting other tissues and organs.
Type I diabetes currently requires regular measurements of blood glucose and insulin injections. Even with more advanced techniques, such as insulin pumps, there is still a lifetime load for these patients. Pancreatic islet transplantation could change this by providing long-term control of blood glucose levels, but the technique is still hampered by the immune rejection of the transplanted tissue.
Common immunosuppressants, such as rapamycin, do not currently work to adequately protect islets, at least in safe doses. The side effects of these 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 usually given at low doses and by specific routes of administration, mainly orally,” said Evan Scott, a researcher involved in the study. “But in the case of a transplant, you need to give enough rapamycin to systematically suppress T cells, which can have significant side effects such as hair loss, mouth ulcers, and a weakened overall immune system.”
To address this, researchers at Northwestern University used nanoparticles to specifically target rapamycin to antigen-presenting cells in the immune system, rather than the T cells it normally affects. This results in more controlled immunosuppression that appears to balance the protection of transplanted pancreatic islets with a reasonable safety profile.
“We asked ourselves, can rapamycin be redesigned to prevent nonspecific T cell suppression and instead stimulate a tolerogenic pathway by delivering the drug to different types of immune cells?” said Scott. “By changing the types of cells targeted, we actually changed the way immunosuppression was achieved.”
To date, researchers have tested the technique on diabetic mice that had received a pancreatic islet transplant. Surprisingly, the mice showed minimal side effects, but did not suffer from diabetes during the 100-day experiment, suggesting that the treatment worked to protect the islets.
Study a Nature Nanotechnology: Subcutaneous nanotherapy reuses the immunosuppressive mechanism of rapamycin to improve the viability of grafting allogeneic islets
