The first clinical trial of a novel therapy that might be able to reverse Type I diabetes will soon be getting under way at Children's Hospital and the University of Pittsburgh Medical Center.
The technique uses the patient's own cells to block the immune system's attack on insulin-producing cells of the pancreas, giving the organ time to repair the damage and resume normal function, explained investigator Dr. Massimo Trucco, director of Children's immunogenetics division.
"If it works, [patients] will be cured," he said. "It will be their own cells, so we don't plan to use any immune suppression or any drug."
The U.S. Food and Drug Administration recently gave the green light for the study, in which 15 adults who have had Type I, or juvenile, diabetes for at least five years will be treated with Dr. Trucco's technique.
"That will be just to prove the approach is safe, not to really cure them," he said. People with established diabetes are unlikely to get better, but their experiences will indicate whether there are any problems with the procedure, such as rashes or allergic reactions.
A similar approach has already been safely used in cancer treatment, Dr. Trucco noted.
If all goes well, the second phase of study will test the technique in perhaps two dozen patients who have been newly diagnosed with Type I diabetes and still have insulin-secreting cells that can be rescued.
First, researchers will take the patient's blood to collect, isolate and purify from it millions of immune cells called dendritic cells. These cells show the immune system's T-cells what antigens, or targets, to look for in their surveillance of the body.
In the lab, the dendritic cells will be loaded with three synthetic molecules that block certain T-cell signals. Instead of becoming activated against the pancreatic cells, the immune cells will call off their attack, Dr. Trucco explained.
The treated cells will then be injected near lymph nodes under the patient's skin in the lower abdomen to intercept T-cells on their way to the pancreas.
In the future, the dendritic cells may also be given a piece of the insulin molecule as a target to better direct the cells to the pancreas.
In mouse experiments, once the T-cells were no longer killing the insulin-producing cells, the pancreas could slowly but surely regenerate. The animals got four to six injections over the course of several weeks, and didn't become diabetic again.
Patients will also get multiple injections over time, but only one blood collection will be needed to gather a sufficient number of dendritic cells. It's not yet known if the effect will be as dramatic or long-lasting in humans as it was in mice, Dr. Trucco said.
He is also working on ways to stimulate the recovery of insulin-producing cells in people who have long-standing Type I diabetes.
Anita Srikameswaran can be reached at firstname.lastname@example.org or 412-263-3858.