Immunosuppression refers to the suppression of the activity of the immune system, thereby curtailing its ability to fight infection. Immunosuppression can be induced by medications known as immunosuppressants.
How do immunosuppressants work?
LEMS is an autoimmune disease caused by the body’s immune system mistakenly attacking the nerve cell endings, leading to the destruction of calcium channels that release the neurotransmitter, or cell-signaling molecule, acetylcholine. Low levels of acetylcholine result in poor muscle contraction leading to symptoms including muscle weakness, pain, breathing problems, constipation, vision problems, and erectile dysfunction.
Immunosuppressants work by suppressing the activity of the immune system so that the autoimmune attack on the nerve cell endings is reduced.
What are the immunosuppressants used to treat LEMS?
Some of the immunosuppressants being used for LEMS therapy are:
Prednisone is an artificial corticosteroid hormone that is similar in action to the adrenal hormone cortisol. Prednisone acts by suppressing the production of antibodies by the B cells of the immune system, thus preventing the attack on the nerve cell endings.
Prednisone is often administered in combination with azathioprine and is a long-term LEMS therapy, lasting between one and four years.
Rituximab is a monoclonal antibody directed specifically against a B cell surface protein called CD20. The binding of rituximab to CD20 results in the lysis, or disintegration, of B cells and reduces the autoimmune attack on the nerve cell endings.
Rituximab still needs to be evaluated in clinical trials for LEMS, but research has shown it can be effective in alleviating symptoms when prescribed off-label to patients with LEMS.
Mycophenolate is an immunosuppressant that works by inhibiting the function of an enzyme called inosine monophosphate dehydrogenase (IMPDH), specifically IMPDH2. IMPDH2 is required for the synthesis of DNA and RNA, a temporary copy of a gene from which protein is made, in T and B cells of the immune system. The inhibition of IMPDH2, therefore, prevents cell division (as DNA synthesis is required for cell division) and protein synthesis. Ultimately the number of T and B cells are reduced, dampening the immune system.
Mycophenolate is often used to prevent organ rejection in transplants, but has yet to be evaluated in clinical trials specifically for LEMS patients. However, the effectiveness of mycophenolate has already been evaluated in other autoimmune diseases such as systemic lupus erythematosus, Crohn’s disease, and dermatitis, suggesting that it could also be effective in LEMS.
Azathioprine is another immunosuppressant that acts by inhibiting cell division. Azathioprine is converted by the body into a compound called 6-mercaptopurine that inhibits DNA synthesis, which subsequently affects cell division.
Azathioprine has not been evaluated in LEMS clinical trials but has been shown to be effective in combination with prednisolone over a period of 6.4 years in a study involving LEMS patients without small cell lung cancer (SCLC).
Last updated: Sept. 19, 2019
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