Feinstein Institute for Medical Research researchers published data yesterday in the Journal of Experimental Medicine that shows the class of drugs commonly used to treat hypertension, ACE inhibitors, can block cognitive decline in mice and might therefore be used to preserve the memory of patients living with lupus.
Lupus is a complex autoimmune disease that arises when the body starts to make antibodies that target its own, healthy cells, often specifically recognizing DNA. Patients can suffer a wide variety of symptoms, but as many as 90 percent develop neuropsychiatric lupus, which is often characterized by cognitive impairments such as memory loss or confusion.
After discovering that the activation of brain cells called microglia likely contributes to the memory loss and other cognitive impairments suffered by many patients with lupus, Betty Diamond, MD, and other Feinstein Institute colleagues wanted to find a way to block microglia. ACE inhibitors are known to block the activation of microglia. In their study with mice, Diamond and colleagues found that the ACE inhibitor captopril protected neurons against activated microglia, preserving their function and the cognitive performance of the mice.
“Our study suggests that ACE inhibitors are a promising class of therapeutics that can easily move into clinical trials aimed at mitigating the cognitive dysfunction associated with neuropsychiatric lupus,” said Diamond, professor and head of the Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute.
More details about the study: Lupus patients experiencing memory loss often produce DNRAbs that recognize both DNA and a critical brain protein called the NMDA receptor, NMDAR. Antibodies are usually unable to enter the brain, but after injury or infection DNRAbs are thought to gain temporary access to the brain where they can target neurons expressing NMDAR. This causes the neurons to die or lose the synapses that connect them to neighboring nerve cells, resulting in memory loss or other cognitive defects. After suspecting that brain cells called microglia might be responsible for trimming the connections between neurons after exposure to DNRAbs, Diamond and colleagues analyzed mice that produce DNRAbs capable of penetrating the brain and inducing memory loss. The researchers found that microglia are activated when DNRAbs enter the brain and that a protein called C1q attracts microglia to the synapses of neurons targeted by these antibodies. Deleting the C1q protein, or depleting the microglial cells themselves, prevented neurons from losing their synapses after exposure to DNRA"
“Betty Diamond is a leader in discovering novel therapeutics that will benefit generations of patients living with autoimmune disease,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institute. “This paper is another important step in her approach to using basic science mechanisms to find future cures.”
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About the Feinstein Institute
The Feinstein Institute for Medical Research is the research arm of Northwell Health, the largest healthcare provider in New York. Home to 50 research laboratories and to clinical research throughout dozens of hospitals and outpatient facilities, the Feinstein Institute includes 4,000 researchers and staff who are making breakthroughs in molecular medicine, genetics, oncology, brain research, mental health, autoimmunity, and bioelectronic medicine – a new field of science that has the potential to revolutionize medicine. For more information about how we empower imagination and pioneer discovery, visit FeinsteinInstitute.org.
About the Journal of Experimental Medicine
The Journal of Experimental Medicine (JEM features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM makes all of its content free online no later than six months after publication. Established in 1896, JEM is published by Rockefeller University Press. For more information, visit jem.org.
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