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Research Sheds Light on Targeting Memory T-Cells in Type 1 Diabetes

by Kathy Jones on  September 23, 2013 at 8:02 PM Diabetes News   - G J E 4
Some promising results from the T1DAL study (Targeting effector memory T cells with alefacept in new onset type 1 diabetes) are published in the latest issue of The Lancet Diabetes & Endocrinology. The study was led by Mark R. Rigby MD, PhD from Indiana University and Riley Hospital for Children in Indianapolis and sponsored by the Immune Tolerance Network (ITN) with additional support from JDRF.
 Research Sheds Light on Targeting Memory T-Cells in Type 1 Diabetes
Research Sheds Light on Targeting Memory T-Cells in Type 1 Diabetes
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Alefacept, an engineered fusion protein targeting a surface molecule, CD2, found on T-lymphocytes, was the first biologic therapy approved for moderate to severe plaque psoriasis. By binding CD2, alefacept inhibits co-stimulation and induces T-cell depletion. T-cell mediated destruction of insulin producing pancreatic beta cells is a central feature of Type 1 diabetes, but targeting of CD2 has not previously been evaluated in this disease. The T1DAL trial was designed to test whether alefacept would preserve pancreatic beta cell function in newly diagnosed patients.

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The Phase II T1DAL study enrolled 49 new-onset type 1 diabetic subjects, ages 12 to 35, who were randomized into two groups: 33 to alefacept and 16 to placebo. Patients received two twelve week courses (separated by a 12 week pause) of either alefacept or placebo. Twelve months from the start of the study, patients underwent a mixed meal tolerance test to measure the C-peptide response (a measure of insulin production). The primary endpoint, a 2-hour C-peptide response, did not show statistically significant differences between treatment and placebo groups; however, a secondary endpoint, a 4-hour C-peptide response, was significantly higher at 12 months in the treatment group compared to the placebo group. Other secondary endpoints including insulin use and rate of hypoglycemic events were significantly lower at 12 months in the alefacept treated group.

Although the primary endpoint was not met, these encouraging results of key secondary endpoints suggest a disease-modifying effect of alefacept. Additional support for alefacept's therapeutic role comes from analysis of T-cell subtypes of treated patients that showed that effector T cells were primarily targeted while sparing protective regulatory T cells. Lead investigator Dr. Mark Rigby suggests, "The T1DAL study is the first to use an agent to specifically deplete the cells which attack the pancreas in type 1 diabetes, the memory and effector T cells. We also found that regulatory T cells are not depleted with this therapy, suggesting that immune re-education can take place."

Longer 24 month follow-up of the subjects in this study is in progress to evaluate the potential for durable efficacy of the alefacept treatment. "Unfortunately our study was not able to enroll the goal number of participants due to drug availability which prevented more definitive conclusions at this point," said Dr. Rigby. "We are eagerly awaiting additional data over the next year which will help us determine if targeting memory T cells will help those with Type 1 diabetes make insulin for extended periods."

About The Immune Tolerance Network
The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit www.immunetolerance.org for more information.



Source: Newswise
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