Feinstein Institute discovers potential of ACE inhibitors in preventing memory loss in lupus patients

New York-based Feinstein Institute for Medical Research finds that ACE inhibitors can prevent cognitive decline in lupus patients, according to a study published in the Journal of Experimental Medicine.

Researchers at the Feinstein Institute for Medical Research in New York have made a groundbreaking discovery that ACE inhibitors, commonly used in the treatment of hypertension, could also benefit patients suffering from lupus by preventing memory loss. This significant finding was detailed in a recent publication in the Journal of Experimental Medicine, which highlights the potential for ACE inhibitors to prevent cognitive decline observed in animal models.

Lupus, a complex autoimmune disease characterized by the body’s immune system attacking its own tissues, often results in cognitive impairments such as memory loss or confusion. These symptoms arise because the immune system mistakenly targets healthy cells, specifically recognizing DNA components in these cells.

The research team, led by Betty Diamond, professor and head of the Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases at the Feinstein Institute, discovered that ACE inhibitors can prevent the activation of microglia—a type of brain cell. Activated microglia contribute to memory loss and other cognitive abnormalities commonly seen in lupus patients. The study specifically highlighted that an ACE inhibitor known as captopril was effective in protecting neurons from the detrimental effects of activated microglia in 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,” stated Betty Diamond regarding the potential applications of their findings.

The study also explored the mechanisms behind cognitive decline in lupus, noting that patients with the condition often produce antibodies called DNRAbs, which target DNA and a critical brain protein, NMDAR (a NMDA receptor). Normally, these antibodies do not cross into the brain; however, following an infection or injury, DNRAbs may gain temporary access, attacking neurons that express NMDAR. This leads to neuron damage or synaptic loss, manifesting as memory loss or cognitive impairment.

Further experiments revealed that when DNRAbs penetrate the brain, microglia are activated, and a protein called C1q attracts these cells to the synapses of the targeted neurons. The Feinstein team found that removing the C1q protein or depleting the microglial cells could prevent the loss of neuronal synapses after exposure to DNRAbs.

This research not only opens the door to potential new treatments for lupus-related cognitive issues but also highlights the Feinstein Institute’s role in pioneering studies that address unmet medical needs in autoimmune diseases.