The treatment that works is a monoclonal antibody, a genetically engineered molecule designed to stop the attack the body's immune system mistakenly mounts against beta cells, which produce insulin. Just one two-week course of injections stopped progression of juvenile, or Type I, diabetes in its early stages in most patients with a minimum of side effects, says a report in tomorrow's issue of the New England Journal of Medicine.
The treatment that doesn't work, described in the same issue of the journal, is an injection of insulin itself to prevent diabetes in people at high risk of the disease. In this case, experts say, the success is the ability to single out people at greatest need of preventive treatment -- something that will be of enormous help when a true preventive measure enters clinical practice.There are high hopes the monoclonal antibody could be that treatment, but a lot of work remains to be done, says Dr. Kevan C. Herold, an associate professor of clinical medicine at Columbia Presbyterian Medical Center in New York City.
The trial results reported in the journal represent a promising start, Herold says. It was done with 24 patients who had just been diagnosed with juvenile diabetes. Half got the monoclonal antibody, which was developed by Dr. Jeffrey Bluestone of the University of California at San Francisco, and half didn't.
After one year, nine of the 12 people who got the treatment were still producing a lot of insulin, compared to just two of the 12 who did not get the treatment.
The results have improved in terms of both numbers and time, Herold says. The study now includes 46 patients and "the results look as good as, if not better than, for the first group of patients," he says. In the early group, "the effect lasts for more than a year. We're not far enough along to say whether it will last two years."
Several trials to explore the monoclonal antibody therapy further are under way or in the planning stage. One of them will try to determine whether multiple injections will improve the results; patients will get three courses of treatment over one year. Another will be an expanded version of the first trial. One reason why it is important is that it will be designated a Phase III trial, the kind whose results can be submitted to the U.S. Food and Drug Administration (FDA) to get approval for clinical use.
"We'll know in two or three years how that trial comes along," Herold says. While he adds that he can't predict what the FDA will do, "if it shows that the drug effect is prolonged indefinitely, I would move very quickly on this."
One point in favor of the treatment is that it has minimal side effects, Herold says. Previous attempts to stop the immune system attack on beta cells have used powerful drugs such as cyclosporine, which has widespread activity. The monoclonal antibody is designed to inactivate a specific receptor on the T-cells that mount the autoimmune attack.
"This is a fundamentally different approach," Herold says. "This is a very specific, targeted approach to immune regulation."
One reason why the monoclonal antibody report is important, says Dr. Robert Goldstein, chief scientific officer of the Juvenile Diabetes Research Foundation, is that "it is really the first time that we have been able to take observations in animals, and do the same thing in people. This gives us at least a possibility of altering the course of the disease in relatively non-toxic fashion."
Goldstein says it is not time to abandon hope that insulin treatment could help prevent the disease. The new study used insulin injections, but another study, using oral insulin, is ongoing.
The value of the study is that the researchers were able to screen more than 84,000 close relatives of people with diabetes and determine that 372 of them, whose average age was 11 years, had at least a 50 percent risk of developing diabetes.
"To identify people at risk way before they got the disease, that hadn't been done before," Goldstein says. In those who got insulin and those who didn't, the rate of developing diabetes was the same, about 15 percent a year.
"If the study had prevented diabetes, that would be a banner headline," Goldstein says. "As it was, it created a lot of good things."
What To Do
You can get information on juvenile diabetes, which affects about 1 million Americans, from the Juvenile Diabetes Research Foundation or the National Institute of Diabetes and Digestive and Kidney Diseases.