Can "borrowed" drugs for treating other diseases protect the skin in patients with lupus? Can researchers coax the body to weed out harmful immune cells that drive tissue destruction in lupus? Those are just two of the innovative approaches for lupus therapies recognized by the Lupus Research Alliance with the latest round of its Target Identification in Lupus (TIL) grants. Seven outstanding scientists from across the United States will receive awards worth up to $600,000 for research projects designed to test promising strategies for treating lupus.
MINING EXISTING DRUGS FOR NEW LUPUS THERAPIES
Will a treatment inspired by malaria drugs work against lupus?
Keith Elkon, MD, University of Washington, will use his TIL grant to further investigate the safety and effectiveness of a promising lupus drug he and his colleagues developed. Dr. Elkon and his team had found that certain treatments for malaria reduced production of type I interferons, immune system molecules which promote inflammation. However, these drugs can be toxic and have other limitations. Dr. Elkon and his colleagues designed a better drug they call X6. If X6 performs well in tests on human cells and mice, they will apply for permission from the Food and Drug Administration to begin clinical trials.
Are old drugs the next lupus treatments?
David Levy, PhD, New York University School of Medicine, will use his TIL grant to investigate whether several drugs for treating other diseases are possible lupus therapies. He is looking for a safe way to block the effects of type I interferons without undermining patients' ability to fight infections.
Can drugs prevent immune cells from invading the skin?
With her TIL grant, Jillian Richmond, PhD, University of Massachusetts Medical School, will test several drugs in mice, including two that are already approved for other diseases, to find out whether they protect the skin. If any of these drugs work in the mice, researchers could test them in people with lupus skin symptoms.
PREVENTING IMMUNE SYSTEM ERRORS THAT LEAD TO LUPUS
How can we remove autoreactive cells in lupus?
With his TIL grant, Eric Meffre, PhD, Yale University, will investigate whether a protein called PTPN22 promotes the production of defective B cells that can attack the body's own tissues.
He will also test mice with lupus to see if inhibiting PTPN22 allows the animals to eliminate these autoreactive B cells, what happens in people who don't have lupus. The results of his research might reveal whether PTPN22 is a good target for development of new drugs to treat lupus.
Can we protect B cells from a bad influence?
Deepak Rao, MD, PhD, Brigham and Women's Hospital, also focuses on why B cells destroy patients' own tissues. Before B cells launch these attacks, they interact with immune cells known as helper T cells. With his TIL grant, Dr. Rao will investigate whether a specific type of helper T cells known as T peripheral helper cells are responsible for leading B cells astray. This work could reveal a new approach to prevent B cells from harming patients' tissues.
Can we switch off helper T cells that promote lupus?
Joseph Craft, MD, Yale University, will use his TIL grant to better understand the role of a protein known as NFAT that acts as a master switch in follicular helper T cells, a type of helper T cells that interact with harmful B cells. Dr. Craft will also test if calcineurin inhibitors, drugs under development for lupus nephritis, to work by blocking follicular helper T cells. The results of the proposed studies could also help pinpoint new molecules that might be therapeutically targeted in lupus.
Do carbohydrates lead to mistaken identity in lupus?
Lupus results from a case of mistaken identity--immune cells attack the body's normal cells as if they were invading microbes. Nan Yan, PhD, University of Texas Southwestern Medical Center, will use his TIL grant to test whether immune cells make this error because they confuse the carbohydrates on patients' cells for the carbohydrates of microbes. His research could lead to new targets for lupus treatments as well as new techniques for diagnosing the disease.
Only one new lupus drug has been approved in more than 60 years. The TIL grants are intended to change that by allowing researchers to pursue promising avenues that could lead to new treatments and a possible cure for lupus. If the current projects prove successful, at least three could directly lead to clinical trials in patients with lupus while others pave the way for the next wave of lupus treatments.
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