For lupus patients, a possible ACE in the hole

The mouse that remembered: ACE inhibitors sustained cognitive functions in laboratory mice with lupus -- suggesting the common pharmaceuticals might do the same for human patients suffering lupus-related memory loss, according to Feinstein Institute scientist Betty Diamond.
By GREGORY ZELLER //

A common pharmaceutical treatment for hypertension could be the key to preserving brain function in lupus patients.

So says data published this month in the Journal of Experimental Medicine by an international team of scientists led by the redoubtable Betty Diamond, head of the Feinstein Institute for Medical Research’s Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases and a professor of molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell.

According to the research, ACE inhibitors – a class of drugs used primarily to treat high blood pressure – can block cognitive decline in mice, suggesting they might also be used to preserve the failing memory of patients living with lupus, a systemic autoimmune disease in which the immune system mistakenly attacks the body’s healthy tissue.

Lupus patients can suffer a wide variety of symptoms. But some 90 percent develop neuropsychiatric lupus, which is usually characterized by cognitive impairments – memory loss, confusion and language difficulties, for starters.

Recognizing that the activation of microglia – which represent about 15 percent of all brain cells and play a key role in overall brain maintenance – likely contributes to the cognitive impairments, Diamond et al looked into ways of blocking microglia activation in lupus patients.

Betty Diamond: Of mice and neurons.

They turned to angiotensin-converting-enzyme inhibitors, which relax blood vessels and are used most often to treat hypertension and congestive heart failure. In a study involving mice, Diamond and her colleagues found that the ACE inhibitor captopril protected neurons against activated microglia – preserving the neurons’ function and the mice’s cognitive performance.

That suggests “that ACE inhibitors are a promising class of therapeutics” in the fight against lupus-related cognitive dysfunction, according to Diamond, an immunologist and longtime lupus researcher who also directs the Zucker School’s PhD program.

And because ACE inhibitors like captopril have already run the gauntlet of human testing and FDA approvals, they “can easily move into clinical trials aimed at mitigating the cognitive dysfunction associated with neuropsychiatric lupus,” Diamond added.

More information on the Journal of Experimental Medicine article – which was authored by Diamond and 13 of her closest friends, representing the Feinstein Institute, Harvard Medical School, Temple University’s Lewis Katz School of Medicine and the Kitasato University School of Medicine and Hokkaido University Graduate School of Medicine, both in Japan – is available here.