Patients who underwent a procedure to wipe out the immune system and reconstitute it with their own stem cells remained insulin injection-free for up to three to four years after the procedure, according to a study published this week in the Journal of the American Medical Association. The research provides further evidence that a stem-cell transplant can reverse type 1 diabetes in some patients. Although a stem-cell transplant is a drastic procedure with a risk of serious side effects, this represents the most successful treatment to reverse the disease in humans without the need for ongoing medication.
The report extends research published in 2007 showing that the majority of 15 patients who underwent a blood stem-cell transplant were able to remain insulin-free for more than 18 months. Richard Burt, a coauthor of the study and a specialist in autoimmune disease at Northwestern University, says that “the criticism of the prior study was that maybe this was some kind of extended honeymoon”; he’s referring to a phenomenon in which patients newly diagnosed with type 1 diabetes will see their symptoms improve temporarily as they make health changes. This latest study extends the treatment to an additional five patients and shows that most patients have been able to remain off insulin for a longer period of time. In addition, it shows that patients have increased levels of a biological indicator of insulin secretion–evidence that they are indeed producing insulin on their own.
Type 1 diabetes is a chronic disease in which the immune system attacks the insulin-secreting beta cells in the pancreas; the body eventually fails to produce enough insulin to control blood-sugar levels. Because this form of diabetes is an autoimmune disease, scientists have been looking for ways to stop the immune system’s destructive actions. One idea is to “reset” the patient’s immune system by wiping it out with drugs and then rebuild it with the patient’s own stem cells. Blood or hematopoietic stem cells reside in the bone marrow and are responsible for replenishing blood and immune-system cells. Hematopoietic stem-cell transplant is most often used to treat patients with cancers like leukemia and other diseases of the blood, but it has recently been investigated as a way to treat several autoimmune diseases, including diabetes and lupus.
In this study, which was based at the University of Sao Paulo, in Brazil, patients first underwent drug treatments to boost their blood stem-cell production, making it possible to harvest stem cells from the blood rather than from the bone marrow. The patients were then hospitalized and given chemotherapy that severely impaired their immune systems; they simultaneously received drugs to prevent infections. The stem cells were purified from the blood and then injected back into the patients, where they could travel to the bone marrow and rebuild the immune system.
Twenty of 23 patients were able to go off insulin treatment for an average of 31 months; 12 of those have maintained this state, while 8 relapsed and began taking low doses of insulin. The researchers also measured levels of C-peptide, a by-product of insulin production that is used as an indicator of how much insulin is being manufactured in the pancreas. Burt explains that even on a “honeymoon” period, C-peptide levels will decrease in diabetics, but for patients in this study, “C-peptide levels kept going up and hit their maximum at two to three years.”
A stem-cell transplant would only be effective in newly diagnosed patients who still have some beta cells left to preserve. Some patients have also achieved insulin independence with an experimental treatment that involves transplanting insulin-secreting cells from a donor. However, these patients require immunosuppressive drugs to keep their immune systems from rejecting the donor cells. “This is the first treatment that, after one treatment, patients are on no insulin and require no medications,” Burt says.
Gordon Weir, head of islet transplantation at Joslin Diabetes Center in Boston, says that the results are impressive and that the treatment is “clearly having some effect on the natural course of the type 1 diabetes,” but it’s still too soon to declare this a permanent cure. Furthermore, he says that excitement about the results should be tempered by concerns about the potential dangers of the treatment and confusion about how the stem-cell transplant is actually working. In this study, two patients developed pneumonia because of the treatment; three others later experienced hormonal disorders, and nine patients developed a sperm deficiency.
Weir points out that the treatment regimen involved many drugs–including powerful chemotherapy agents–which may also have affected the diabetes. “We don’t actually know the stem cells had anything to do with this result,” he says. Weir hopes that the trial will spur further studies on the role of the stem cells and ways to make the treatment safer. Burt and his colleagues are now awaiting FDA approval for a randomized trial that would provide more rigorous data about the benefit of this treatment for diabetes.