Combination Therapy Fails to Reverse Autoimmune Attack in Type I Diabetes

Nine TID subjects were treated with rapamycin orally for three months and IL-2 three times per week for one month. Beta cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses.

Rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B cells by inhibiting their response to IL-2. IL-2 is necessary for the growth, proliferation, and differentiation of T cells to become "effector" T cells. IL-2 is normally produced by T cells during an immune response. This cytokine, which is normally produced by T cells during an immune response, is necessary for the growth, proliferation, and differentiation of T cells to become effector T cells.

The rationale behind the treatment regimen was that although the body's immune system attacks and destroys the insulin-producing beta cells in the pancreas, a small number of viable beta cells may remain in many individuals that could be rescued as a partial therapeutic approach.

However, results of the study published in the June 20, 2012, online edition of the journal Diabetes revealed that while regulatory T cells (Tregs) increased within the first month of therapy, clinical and metabolic data demonstrated a transient worsening in the condition of all subjects.

The temporary impairment of beta cell function led to the conclusion that this drug combination was not having the desired overall effect. Monitoring of the insulin production in the nine subjects indicated that the beta cell preservation goal was not achieved, and the study was therefore terminated. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.

“This study result has been extremely important to scientists looking for ways to stop the immune attack,” said senior author Dr. Carla Greenbaum, director of the diabetes research program at Benaroya Research Institute. “Our aim would be to harness the good effects of this therapy while preventing the bad effects. Participants who have not yet completed the study will continue to be followed.”

Related Links:
Benaroya Research Institute