Research by the Faustman Lab
Overview
For over 15 years, the Faustman laboratory has pursued the reversal of established autoimmunity as the prerequisite to successful treatment of type 1 diabetes and other autoimmune diseases. The Faustman lab's goal is to investigate treatments that permanently eliminate underlying disease, not just manage symptoms. This work has led to the discovery of a novel way to permanently reverse type 1 diabetes in diabetic mice. Currently, Dr. Faustman and her colleagues are working on strategies to translate this research to human diabetics. In 2008, a human clinical trial will begin testing one part of the potential therapy in human diabetics.
In addition to working to bring a potential treatment for type 1 diabetes to humans, another goal is to identify new treatments for multiple autoimmune diseases. Significant evidence exists to suggest that other autoimmune diseases with similar cellular defects as those seen in type 1 diabetes- including Crohn's disease, lupus, scleroderma, Sjogren's syndrome, rheumatoid arthritis, and multiple sclerosis- can benefit from the approach the Faustman lab has developed for type 1 diabetes.
Research History
Over the past decade, the Faustman lab has focused on protein defects specific to pathogenic white blood cells. In her research, Dr. Faustman discovered that in the spontaneously diabetic non-obese diabetic (NOD) mouse and in the diabetic human, the pathogenic lymphoid cells have a defect (disruption of the NFkB signaling pathway) that makes them sensitive to death in the presence of certain levels of tumor necrosis factor-alpha (TNF-a). In research published in 2001 in the Journal of Clinical Investigation and in 2003 in Science, Dr. Faustman and colleagues used a brief, non-toxic treatment to induce TNF-a in end-stage diabetic mice and permanently eliminate their disease. This therapeutic approach not only stopped the autoimmunity and restored normoglycemia, but also precipitated the regeneration of insulin-producing cells without the introduction of stem cells.
The 2003 Science paper also identified a potential new source of adult stem cells- the spleen- that could form new islets in formerly diabetic animals and speed disease reversal and regeneration. However, reversal was also seen in those animals that did not have live spleen cells introduced. There is no intent of spleen cell transplants for human patients. Dr. Faustman and colleagues hope there is sufficient regeneration and rescue to not require any transplant.
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