A significant breakthrough in the fight against lupus, an autoimmune disease that impacts 1.5 million Americans, has been made by a team of scientists from Northwestern Medicine and Brigham and Women’s Hospital.
The team believes they have not only identified the cause of lupus but may also have found a potential cure or at least a more refined treatment. They are now working on developing a pharmacological method to deliver what they describe as a “cure-like molecule.”
Lupus erythematosus, commonly known as lupus, is a complex autoimmune condition in which the body’s immune system mistakenly attacks its own tissues, leading to a range of complications. These can vary from skin issues to potentially life-threatening damage to vital organs such as the heart, kidneys, and brain. The precise cause of lupus has long remained elusive, and current treatments, while somewhat effective, are often criticized for their lack of precision.
“Up until this point, all therapy for lupus is a blunt instrument. It’s broad immunosuppression,” said co-corresponding author Dr. Jaehyuk Choi, associate professor of dermatology at Northwestern University. “By identifying a cause for this disease, we have found a potential cure that will not have the side effects of current therapies.”
The research team began their investigation by analyzing the immune responses of lupus patients. They discovered that individuals with lupus had abnormally high levels of a protein known a interferon, which is typically involved in the body’s defense against infections. At the same time, these patients had insufficient levels of a receptor called aryl hydrocarbon receptor (AHR), which plays a crucial role in regulating how the body responds to infection.
This imbalance in the immune system, particularly the lack of AHR activity, appears to be a key factor in the development of lupus. The researchers found that when the AHR pathway is underactive, it leads to an overproduction of immune cells that generate autoantibodies, the harmful agents that attack the body’s own tissues in lupus patients.
Dr. Deepak Rao, a rheumatologist at Brigham and Women’s Hospital and co-corresponding author of the study, explained the potential impact of their findings. “We’ve identified a fundamental imbalance in the immune responses that patients with lupus make, and we’ve defined specific mediators that can correct this imbalance to dampen the pathologic autoimmune response,” said Dr. Deepak Rao.
In essence, their discovery offers a way to rebalance the immune system in lupus patients by restoring AHR activity. This could dramatically reduce the production of the harmful autoantibodies that cause the disease’s debilitating symptoms. The team’s goal is to develop drugs that can activate the AHR pathway effectively and safely in lupus patients.
According to the Northwestern, to further validate their findings, the researchers conducted tests where they reintroduced AHR-activating molecules into blood samples from lupus patients. Interestingly, this intervention appeared to “reprogram” the lupus-causing cells, transforming them into a type of cell that could promote healing rather than harm. This reprogramming suggests that activating the AHR pathway could help reverse the damage caused by lupus.
“We found that if we either activate the AHR pathway with small molecule activators or limit the pathologically excessive interferon in the blood, we can reduce the number of these disease-causing cells,” said Choi. “If these effects are durable, this may be a potential cure.”
The potential implications of this discovery are enormous. Current lupus treatments often involve broad immunosuppression, which can lead to a range of side effects, including increased susceptibility to infections and other health complications. The possibility of a targeted treatment that corrects the underlying immune system imbalance without broadly suppressing the immune system could represent a significant advancement in lupus care.
As the research progresses, the team is focused on developing and refining these AHR-activating drugs, with the hope of eventually bringing a new, more effective treatment to lupus patients. If successful, this treatment could not only improve the quality of life for millions of people living with lupus but could also pave the way for new approaches to treating other autoimmune diseases.
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