$600K LRA awards go to 7 scientists for work on treatments for lupus

Lupus Mechanisms and Targets Award winners to seek molecular targets

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by Mary Chapman |

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The Lupus Research Alliance (LRA) has announced the latest recipients of its Lupus Mechanisms and Targets Award (LMTA), who will investigate molecular pathways or targets that could lead to new or better treatments for lupus.

Each of the seven awarded scientists will receive up to $600,000 in funding over three years.

“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,” Teodora Staeva, PhD, LRA’s chief scientific officer, said in an organization press release.

Three of the researchers will focus on lupus nephritis, which is kidney inflammation caused by the autoimmune disease that can result in organ damage. Two others will investigate “novel therapeutic frontiers” based on disease mechanisms. One investigator will focus on lupus’ impact on pregnancy, while another will try to engineer patients’ own immune cells as a potential treatment strategy.

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In lupus, the immune system attacks the body’s own healthy tissues. Immune B-cells produce self-reactive antibodies, or autoantibodies, that play a major role in launching this attack.

It is unknown what prompts the attack that causes lupus to begin. But the disease can result in a broad range of symptoms, from skin issues to kidney and bladder inflammation to problems with joints, muscles, and bones, among others.

The chief aim of current treatments for lupus is to mitigate the autoimmune response that causes the disorder, with the goal of controlling the disease’s symptoms and preventing organ damage.

But the development of targeted therapies is hampered by an incomplete understanding of lupus, according to the LRA, which stated in the release that the awarded research could potentially “revolutionize” the field.

This year’s LMTA recipients under the category of “Uncovering Underlying Factors and Novel Therapeutic Targets for Lupus Nephritis” are Shaun Jackson, MD, PhD, of Seattle Children’s Hospital, Chandra Mohan, MD, PhD, of the University of Houston, and Boris Reizis, PhD, of the New York University Grossman School of Medicine.

Jackson is developing a tool called spatial transcriptomics with the aim of identifying immune cells that could be associated with treatment response. Jackson will do this by using the tool to analyze kidney biopsy samples that will be collected before and after treatment.

Ultimately, Jackson’s research could support the development of targeted therapies, improve therapeutic effectiveness, and enhance the life quality of those with lupus nephritis, a common lupus complication characterized by kidney inflammation and damage.

Mohan, meanwhile, will use her award to determine whether a protein called S100A4 drives fibrosis, or scarring, of kidney tissue associated with end-stage kidney disease. The protein has not yet been studied in lupus nephritis, but its blockage was found to be promising as a way to ease kidney scarring in other models of chronic kidney disease. This research could result in the discovery of a new treatment target that could reduce disease severity and improve survival rates in lupus nephritis.

The other recipient in this category, Reizis, will assess whether factors other than anti-DNA antibodies lead to kidney inflammation. Specifically, Reizis will examine genetic mutations that cause inflammation, bacteria that cause infection, and environmental factors (e.g. UV light exposure) for possible culpability. A better understanding of kidney inflammation and impairment in lupus nephritis could result in improved ways to monitor and predict disease progression.

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Another award grouping is called “Precision Targeting of Harmful B Cells Using CAR-T Cells,” under which Marco Ruella, MD, of the University of Pennsylvania Perelman School of Medicine, will seek to develop a new CAR-T cell therapy.

Many CAR-T treatments target the molecule CD19, found both on healthy and disease-causing B-cells, thus reducing the number of all B-cells. However, this renders the patient vulnerable to infections. Ruella will focus on developing a new CAR-T cell product that spares healthy B-cells, consequently reducing infection risk and potentially improving the lives of those with advanced disease, who have relatively few treatment options.

In the award category “Exploring Therapeutic Targets for Devastating Blood Clotting Disorder in Pregnancy,” Jason Knight, MD, PhD, of the University of Michigan, will seek to determine whether microscopic structures called neutrophil extracellular traps could be targets to treat antiphospholipid syndrome (APS) in pregnant lupus patients. APS is associated with a heightened risk of blood clots and pregnancy loss. His study findings could serve as the foundation for a clinical trial testing colchicine, a safe and inexpensive therapy to help those with APS.

Under “Investigating Novel Therapeutic Frontiers for SLE,” Michael Carroll, PhD, of Boston Children’s Hospital, will test the effectiveness of a therapeutic antibody he developed that blocks B-cell activation to tamp down the production of autoantibodies without depleting B-cells. In his research, Carroll will use a mouse model of lupus and the cells of lupus patients.

Finally, Nan Yan, PhD, of the University of Texas Southwestern Medical Center, will explore how the gene PARP7 lessens type 1 interferon induction and learn whether the gene’s “interferon dimming” effects can be used as a treatment strategy. In lupus, type 1 interferons activate a number of genes, including PARP7. Yan previously learned that the gene acted as a kind of built-in dimmer switch, lessening interferon signaling to avoid immune system overactivation.

The LRA is the largest nonprofit organization focused on funding lupus research on a global scale. Its overarching goal is to revolutionize lupus treatment by funding the most promising and innovative research in the disease, promoting the discovery and development of better diagnostic methods and treatments, and ultimately a cure for lupus.