Updated March 11, 2022
Neuropsychiatric lupus affects 80-90% of people with lupus. In a video series hosted by the Young Leaders Board of the Lupus Research Alliance, Dr. Meggan Mackay explains How to know if you have neuropsychiatric lupus and offers ways to improve cognitive health. Dr. Mackay also describes a clinical trial she is leading in which the LRA is investing $2.5 million to test ACE inhibitors, common blood pressure medications, to prevent brain cell damage in people with lupus. You can talk with your healthcare provider about joining this trial and reference this description on clinicaltrials.gov, the official database of clinical studies conducted in this country provided by the U.S. National Library of Medicine.
Because these ACR inhibitors are already approved by the U.S. Food and Drug Administration and have worked safely for decades, testing them as a treatment for lupus could save considerable time and financial resources. The Phase 2 clinical trial is being conducted through the Lupus Clinical Investigators Network of 57 academic centers managed by the Lupus Research Alliance affiliate Lupus Therapeutics and is actively enrolling patients.
“Mental health in our lupus patients has been ignored for a long time, in part because we have not understood the mechanisms responsible for brain damage caused by lupus and therefore have not had any treatments to offer patients. Thanks to Dr. Diamond’s work showing how activated microglia cells damage neurons in the brain, combined with our brain imaging studies, we have designed a trial that will test whether ACE inhibitors can decrease microglia activation and preserve brain function. We are very excited about this trial for many reasons; most importantly, ACE inhibitors are very safe and, unlike all of the other medications we rely on to treat lupus, they do not suppress the immune system!”
This trial is based on a breakthrough discovery made by Dr. Mackay’s colleague at the Feinstein Institutes for Medical Research and LRA grantee Dr. Betty Diamond in 2004. Dr. Diamond discovered that a subset of antibodies can cause cognitive and emotional alterations in lupus patients if they cross the blood-brain barrier, a protective barrier surrounding the brain. Specifically, Dr. Diamond and her team used a mouse model to show that some lupus autoantibodies attach to neurons in the brain, causing them to die. The dead neurons are then cleared by other cells in the brain, called microglial cells. This “clean up squad” of microglial cells becomes activated, leading them to attack and destroy healthy neurons and synapses (places where neurons communicate with each other) that are necessary for several functions, including generating and retaining memories.
The team then discovered that a common and safe class of medications for blood pressure, ACE inhibitors, also control the activation of the microglial cells.
Using highly sophisticated brain imaging in people with lupus, Drs. Diamond and Mackay found that high levels of the damaging autoantibodies correlated with increased metabolism in specific brain regions and with poor performance on cognitive testing. These studies suggested that the increased brain metabolism was a marker for cognitive impairment related to the damaged neurons and activated microglial cells. Dr. Diamond received the 2018 Lupus Insight Prize from the LRA to continue this work.
All this critical data contributes to the formation of Dr. Mackay’s hypothesis: lupus patients treated with an ACE inhibitor that crosses that blood brain barrier will show significant decreases in brain metabolism after 12 months of treatment compared to lupus patients treated with an ACE inhibitor that does not cross the blood brain barrier. The team will also measure microglial cell activation directly with a different imaging technique and assess improvement in neuropsychological testing.