JDRF Research
Drug Preserves Beta Cell Function in Type 1 Diabetes Patients
JDRF-funded researchers in Europe found that short-term treatment with a drug called an anti-CD3 antibody can preserve pancreatic beta cell function in patients with recent onset diabetes for up to 18 months, decreasing the need for insulin and paving the way for better metabolic control of diabetes.
The finding, reported in the New England Journal of Medicine, could lead to interventions that delay or reduce the risk of type 1 diabetes and related complications such as eye, nerve, and kidney disease.
“These exciting results provide enormous hope that we can preserve residual beta cell function by modulating the autoimmune attack and in fact change the clinical course of type 1 diabetes,” said JDRF Executive Vice President for Research Richard Insel, M.D.
“There is no other current treatment that can actually change the clinical course once the disease has begun. This study shows we are on the right track, and opens the door for researchers to target this treatment specifically to individuals who would receive the most benefit.”
Patients received the anti-CD3 antibody, or ChAglyCD3. Antibodies are proteins produced by the immune system to fight off foreign bodies and infection. After six days of the antibody therapy, patients continued to produce their own insulin and needed less supplemental insulin to maintain normal blood glucose levels compared with patients who received a placebo. This benefit was apparent up through 18 months after the treatment, suggesting the protective effect is lasting — although for how long is not yet known. Moreover, side effects were minor and short-lived, including flu-like symptoms.
The Phase II clinical trial, involving 80 newly diagnosed patients, was conducted in collaboration with a team of clinicians and researchers from France, Belgium, Germany and England. It was led by Lucienne Chatenoud, M.D., Ph.D. of the Hospital Necker in Paris. Dr. Bart Keymeulen (in Brussels) was the clinical coordinator for the trial, which was one of the projects undertaken by the JDRF Center for Beta Cell Therapy in Europe, directed by Daniel Pipeleers, M.D., Ph.D.
This human clinical trial builds on a JDRF study using a similar antibody — published in 2002 by Kevan Herold, M.D., of Columbia University College of Physicians and Surgeons, and Jeffrey Bluestone, Ph.D., director of the JDRF Center for Islet Transplantation at University of California, San Francisco-University of Minnesota.
The European study takes the Bluestone-Herold study — and anti-CD3 research overall — several steps further by involving a much larger group of patients and tracking how much residual beta cell function each patient had at the beginning of treatment. This allowed the researchers to track and compare ChAglyCD3’s effect on patients who had high and low residual beta cell function at the time of the intervention, to see how well the drug worked with patients in both categories.
The research team observed that ChAglyCD3’s protective effect was significant in patients who had higher beta cell function at the time they received the drug. “A tremendous amount of work was put into this study, and I am thrilled with the outcome,” Dr. Chatenoud said. “The team of clinicians and their colleagues who dedicated themselves to this effort are to be commended for their work. These include Dr. Bart Keymeulen and Dr. Chantal Mathieu in Belgium and Dr. Anette Ziegler in Germany, as well as the Belgian Diabetes Registry, all of whom made it possible to recruit the patients. And I would be remiss for not mentioning that the international collaboration within the JDRF Center allowed the researchers to proceed in an efficient manner.”
“JDRF made this possible “ said Dr. Pipeleers. “We can now inform patients that a step has been made towards stopping the disease but we will also have to explain why more work is needed before a treatment will be routinely available for clinical practice.”