NEW YORK, Feb. 28, 2024 /PRNewswire/ — The Lupus Research Alliance (LRA) is pleased to announce the recent recipients of the Lupus Mechanisms and Targets Award (LMTA), whose research will investigate molecular pathways or targets that will lead to new or improved therapies for individuals with systemic lupus erythematosus (SLE). The LMTA provides investigators up to $600,000 over three years.
The development of targeted treatments is hindered by an incomplete understanding of lupus and its devastating complications. These seven talented investigators will identify targets for new treatments and test novel therapeutic avenues to revolutionize the field and improve the lives of individuals with lupus.
“We are thrilled to offer the Lupus Mechanisms and Targets Award to the seven outstanding investigators who will be investigating underlying factors and potential targeted treatment approaches to address the varied and complex needs of people with lupus,” said Teodora Staeva, Ph.D., Chief Scientific Officer of the LRA.
Lupus Mechanisms and Targets Award Recipients
Uncovering Underlying Factors and Novel Therapeutic Targets for Lupus Nephritis
Shaun Jackson, M.D., Ph.D.; Seattle Children’s Hospital
Surgical biopsies of the kidneys are often needed to diagnose lupus nephritis (LN), kidney inflammation caused by lupus that can result in severe and sometimes life-threatening organ damage. However, physicians do not typically repeat biopsies after treatment has begun to assess its effectiveness. Dr. Jackson will apply an innovative tool called spatial transcriptomics to analyze kidney biopsy samples collected before and after treatment to identify which immune cells are associated with treatment response. This study could inform the development of targeted therapies, improve treatment effectiveness, and enhance the quality of life of individuals with LN.
Chandra Mohan, M.D., Ph.D.; University of Houston
End-stage kidney disease, also known as kidney failure, is a major cause of death in SLE. Recent studies have shown that kidney fibrosis (changes in the thickening or scarring of kidney tissue) is associated with end-stage kidney disease. Dr. Mohan will determine whether a protein called S100A4 drives fibrosis. While S100A4 has not yet been studied in LN, blocking S100A4 has shown promise in improving kidney fibrosis in other models of chronic kidney disease. These findings may highlight a new target for therapies that could lessen disease severity and increase survival among people with LN.
Boris Reizis, Ph.D.; New York University Grossman School of Medicine
In SLE, autoantibodies mistakenly bind to a person’s proteins and genetic materials, including DNA, and these antibody-DNA complexes can move to the kidney, where they cause inflammation and impairment, sometimes leading to LN. However, anti-DNA antibodies do not always cause LN, highlighting other poorly understood factors that lead to nephritis. Dr. Reizis will assess how other factors, including genetic mutations that cause inflammation, bacteria that cause infection, and environmental exposures (such as UV light) may cause kidney inflammation so better strategies can be developed to monitor and predict the progression to this serious kidney complication in lupus.
Precision Targeting of Harmful B Cells Using CAR-T Cells
Marco Ruella, M.D.; University of Pennsylvania Perelman School of Medicine
Chimeric antigen receptor T cell (CAR-T) therapy, the engineering of a patient’s own immune cells to recognize and target specific cells, has recently shown profound effects in individuals with SLE. However, many CAR-T therapies target CD19, a molecule found on healthy B cells as well as disease-causing B cells, meaning CD19-targeting CAR-T cell therapy can reduce the number of all B cells and leave the individual vulnerable to infections. Dr. Ruella will develop a new CAR-T cell product that targets a molecule mostly found on disease-causing B cells while sparing healthy B cells, thereby limiting the risk of infection and potentially improving the lives of individuals with advanced disease for whom there are limited treatments.
Exploring Therapeutic Targets for Devastating Blood Clotting Disorder in Pregnancy
Jason Knight, M.D., Ph.D.; University of Michigan
Many individuals with SLE are diagnosed with antiphospholipid syndrome (APS), which causes an increased risk of blood clots and pregnancy loss. Despite advances in its monitoring and treatment, 1 in 8 APS pregnancies will still end in fetal death, underscoring the dire need for better therapies. Dr. Knight will determine whether microscopic structures called neutrophil extracellular traps, or NETs, are a possible target for the treatment of APS in pregnant people. These findings could lay the groundwork for a clinical trial testing a safe and inexpensive drug called colchicine to help people with APS achieve healthy and successful pregnancies.
Investigating Novel Therapeutic Frontiers for SLE
Michael Carroll, Ph.D.; Boston Children’s Hospital
SLE is characterized by autoantibodies that mistakenly target a person’s own cells as foreign pathogens. When autoantibodies, produced by B cells, bind to their target, they form complexes that can cause damage to organs like the kidneys and skin. Therapies that block the source of harmful autoantibodies (like B cells) are needed. Dr. Carroll previously developed a therapeutic antibody that blocks B cell activation to tune down the production of autoantibodies without depleting the B cells. He will now test the effectiveness of this therapeutic antibody in a mouse model of lupus and cells from people with SLE.
Nan Yan, Ph.D.; University of Texas Southwestern Medical Center
A high level of type I interferons (molecules involved in the antiviral response) is one of the most common characteristics of SLE. Type I interferons induce, or turn on, many genes. Dr. Yan recently discovered that one of these genes, PARP7, acts as a “built-in dimmer switch,” reducing interferon signaling to avoid over-activation of the immune system. Dr. Yan will explore how PARP7 reduces type I interferon induction and determine whether the “interferon dimming” effects of PARP7 can be harnessed as a treatment approach.
About Lupus
Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women, often striking during the childbearing years of 15-45. Blacks/African Americans, Hispanics, Asians, and Native Americans are at two to three times greater risk than Caucasians for developing lupus. In lupus, the immune system, meant to defend against infections, produces antibodies that mistakenly recognize the body’s own cells as foreign, prompting other immune cells to attack and potentially damage organs such as the kidneys, brain, heart, lungs, blood, skin, and joints.
About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance’s Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. For more information, please visit the LRA at LupusResearch.org and on social media at: X, Facebook, LinkedIn, and Instagram.
SOURCE Lupus Research Alliance
