Dr. Matthias von Herrath works in dogged pursuit of diabetes
In recent months, La Jolla has been the center of research “firsts” that promise to significantly advance efforts to better understand and ultimately conquer type 1 diabetes. In each case, front and center has been the work of Matthias von Herrath, M.D., director of the Center for Type 1 Diabetes Research, at the La Jolla Institute for Allergy & Immunology.
In December, international headlines were generated with the announcement of von Herrath’s creation of the first real-time movies of the cellular destruction underlying type 1 diabetes in mouse models. This technical feat is already providing never-before insights into the disease. Heretofore, researchers had to extrapolate cellular processes from photos, computer modeling, or lab experiments.
In January, came publication of research findings that identify, in human tissue, the specific immune system T cells that trigger pancreatic beta cell destruction. This validates information previously known only in petri dishes and mouse studies. Moving forward, it provides a focal point for interrupting the disease process.
Type 1 diabetes (so-called juvenile diabetes) results from a self-destructive immune response against the insulin-producing pancreatic beta cells. As a result, patients with type 1 diabetes develop a life-long dependence on insulin-replacement therapy that often brings with it debilitating complications such as heart disease, blindness, and kidney disease.
The cause of type 1 diabetes is unknown. Confounding researchers is that while type 1 diabetes predominantly develops early in life, it can also suddenly strike adults. Also bewildering is that symptoms can at times flare up then get better. This has led researchers to wonder if type 1 diabetes is a true autoimmune disease or “immune-mediated;” triggered by a bacteria or virus in people who are genetically vulnerable to the disease.
“Something else, in addition to genetic factors, renders the pancreas vulnerable (to immune attack),” von Herrath said during a recent Frontiers in Science & Technology forum, sponsored by CONNECT. And, von Herrath’s lab has found that certain viral infections could trigger or dampen the autoimmune response in diabetic cases.
In addition to current insulin-replacement therapy, researchers question whether it’s possible to “reset” the body’s immune system to eliminate beta cells destruction by T cells.
“Life-long immune suppression is difficult to imagine with type 1 diabetes,” said von Herrath. “You cannot take (immune-response cells) out completely.”
Elsewhere, bone-marrow transplantation has been tried with some success, but it does not offer a universal therapy due to its high cost and low success rate (only 30 percent remission in patients after six years). Even attempts to transplant a piece of a healthy pancreas between donors who are twins have only relieved type 1 diabetes symptoms for two to three months.
“(In the future) the goal is a site-specific, antigen therapy with low side effects,” said von Herrath.
A step forward in realizing that goal occurs this summer when von Herrath assumes leadership of a new Seattle-based translational type 1 diabetes center funded by Novo Nordisk, a global healthcare company specializing in diabetes care. The center will focus on the development of type 1 diabetes immunotherapies; von Herrath will continue to lead his current research program at the La Jolla Institute on a part-time basis.
“We are excited by the opportunities that this dual appointment will provide Dr. von Herrath to take his discoveries to the next level – clinical development,” said Mitchell Kronenberg, Ph.D., La Jolla Institute president and chief scientific officer.
“My dream has always been to see the most promising immune-based interventions translated into better treatments for patients with diabetes,” von Herrath said. “As head of the translational center, I will have an opportunity to pursue this dream, as well as forge new public-private collaborations to access other novel research ideas for potential development into better treatment options for people with type 1 diabetes.”
— Lynne Friedmann is a science writer based in Solana Beach.