Northwell Health - Feinstein Institute for Medical Research

Medical advancements can sometimes come from looking at currently approved therapies in a new light. It is this process that led investigators Betty Diamond, MD, leading rheumatologist and researcher, and Yousef Al-Abed, PhD, a molecular chemist, in their search for a better treatment for systemic lupus erythematosus (lupus). They've discovered an HIV medication that could be used to treat and prevent organ damage. Lupus is an autoimmune disease that causes the immune system to lose the ability to differentiate between foreign agents and healthy tissue. It becomes hyperactive and attacks healthy tissue, causing inflammation, swelling, and damage to joints, skin, and internal organs. Current therapies for lupus include immune-suppressing drugs that decrease disease flare ups and organ damage. However, this treatment comes with such side effects as increased risk of infection. Fast-tracked progress In their study, Drs. Diamond and Al-Abed examined therapies for other conditions that could be used to specifically target the molecular mechanisms of lupus that cause organ damage. Identifying a medication that already has FDA approval to treat another condition can help condense the time frame from discovering the drug's effectiveness on a new condition to its actual use in patients, though additional research is needed before it is approved for patients with lupus. "We know that one of the causes of organ damage in patients with lupus is a protein that is part of the immune system called anti-DNA autoantibodies," Dr. Diamond said. "It is our belief that an effective treatment would prevent these anti- DNA autoantibodies from attacking healthy tissue." This study, published in Journal of Medicinal Chemistry, outlines Drs. Diamond and Al-Abed's identification of a select group of HIV medications currently on the market that stop or slow the function of anti-DNA autoantibodies. Their teams reviewed the molecular mechanisms of these medications to find which would help prevent the specific way anti-DNA autoantibodies interact in patients with lupus. Through this work they identified a compound called FISLE-412, shown to decrease binding of anti-DNA antibodies in several experimental models, which in turn reduced organ damage, including in the brain and kidney — both critical to normal bodily function. Feinstein Institute researchers have discovered that an established HIV medication could be repurposed to treat lupus. "Further study is required to test the effectiveness and safety of these therapies, but we believe that targeting anti-DNA antibodies is a novel approach in the treatment of lupus." — Yo u s e f A l - A b e d , P h D, p ro fe s s o r a n d h e a d o f t h e Fe i n s t e i n I n s t i t u t e Ce nt e r fo r M o l e c u l a r I n n ovat i o n What's old is new again FeinsteinInstitute.org 7 Innovation

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