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Immunotherapeutic rescue of steroidogenic function in autoimmune Addison's disease: Pilot Study

Funder: UK Research and InnovationProject code: G0701632
Funded under: MRC Funder Contribution: 149,934 GBP

Immunotherapeutic rescue of steroidogenic function in autoimmune Addison's disease: Pilot Study

Description

Autoimmune Addison`s disease is a chronic disease caused by the body`s immune system attacking and eventually destroying the adrenal glands. This causes deficiency of certain steroid hormones that are essential for life and wellbeing, which the healthy adrenal glands normally produce. The current approach to treating Addison`s disease is simply to replace the missing adrenal steroid hormones using tablets. This makes people feel better, but often not fully back to normal and leaves them chronically dependent upon steroid medications (2 or 3 doses daily), with several long-term side effects, as well as a reduced life-expectancy. We plan a radical new approach to treatment of Addison`s disease, which is to try to switch off the immune system, so the attack on the adrenal glands ceases. We will use a safe but powerful treatment called rituximab that removes a certain type of immune cell, called the B lymphocyte, from the bloodstream and tissues. This treatment has been used on more than a million people with blood conditions over the last 10 years, and is given as two 4-hour infusions, 14 days apart. The results of rituximab therapy in several other autoimmune disease show great promise, with substantial amelioration of disease. As adrenal tissue is already known to have a great capacity for regeneration, it is highly likely that the remaining (not destroyed) adrenal cells will regenerate, restoring the secretion of the vital steroid hormones to normal, once the immune attack has gone. The body naturally makes an adrenal gland stimulating hormone, ACTH-adrenocorticotropic hormone, when adrenal secretions are deficient or below the necessary levels. People with Addison`s have very high levels of ACTH, and this would cause the regeneration of the adrenal glands once the immune attack has been removed. This strategy could lead to a permanent cure of autoimmune Addison s disease, for the first time.

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