LRA funds 4 projects exploring targets of possible lupus treatments

Grants given through LRA's Lupus Mechanisms and Targets Award program

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The Lupus Research Alliance (LRA) is funding four research projects aiming to explore molecular targets that could lead new ways of treating lupus.

The grants were given as part of the LRA’s Lupus Mechanisms and Targets Award (LMTA) program, which offers up to $600,000 over three years for research into disease mechanisms and targets.

“We are proud to be able to offer this financial support, with the ultimate goal of improving outcomes for lupus patients,” Teodora Staeva, PhD, vice president and chief scientific officer of the LRA, said in an association press release.

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Projects may lead to new treatments for lupus and lupus nephritis

The first project is led by Jennifer Anolik, MD, PhD, with the University of Rochester Medical Center in New York. It will test whether sodium-glucose cotransporter-2 (SGLT2) inhibitors can improve outcomes in lupus nephritis, a complication of lupus characterized by kidney inflammation. SGLT2 inhibitors are a class of medications used to help control blood sugar and manage kidney damage in people with diabetes.

Anolik’s project will include experiments to assess whether SGLT2 inhibitors lessen kidney damage and inflammation in mouse models of lupus nephritis, as well as tests into how these medications affect clinical outcomes and immune cell counts in patients.

Another project — led by Michelle Kahlenberg, MD, PhD, with the University of Michigan — will focus on the potential role of a group of proteins, called Hippo proteins, in lupus. Kahlenberg’s previous research suggested that these proteins help to control the production of type 1 interferons, a group of pro-inflammatory signaling molecules implicated in lupus. This project aims to test whether Hippo proteins could be viable therapeutic targets in lupus.

Jillian Richmond, a PhD with the University of Massachusetts Chan Medical School, is leading a third project focusing on the movement of T-cells, a type of inflammatory immune cell involved in lupus activity.

Earlier research led by Richmond showed that T-cells in the skin have a protein receptor called CXCR6 on their surface. This receptor is able to bind to a protein called CXCL16, which is found on skin cells. This project aims to test whether the interaction between CXCR6 and CXCL16 is important for controlling the movement of inflammatory T-cells into the skin of people with cutaneous lupus. The project also will include a veterinary clinical trial targeting CXCR6 and CXCL16 in dogs with skin lupus, to see if a “lasting treatment response” is possible.

The fourth project is being led by Betsy Barnes, PhD, with The Feinstein Institutes for Medical Research in New York. Prior studies have shown that variations in the immune signaling gene IRF5 affect the risk of developing lupus, and that another gene, called STK25, helps to regulate the activity of IRF5.

This project will compare STK25 activity in people with or without lupus, and with or without disease-associated variants in IRF5. Researchers also will explore in more depth how STK25 activates IRF5 in response to inflammatory signals, as well as the potential therapeutic impact of disrupting STK25 in lupus-prone mice.

“These four new LMTA awards support innovative lupus researchers whose work is poised to deliver much needed new information for the lupus field,” Staeva said.