Scripps team spotlights a new lupus drug target

Study authors David Nemazee, Changchun Xiao and Alicia Gonzalez-Martin

A Scripps team has discovered a microRNA molecule that appears to cause the autoimmune disease lupus. This represents a potential drug target that could take current treatments for autoimmune disease beyond simply controlling symptoms.

While the exact cause of autoimmune disease is unknown, it stems from B cells attacking the body's own tissues in addition to attacking antigens. In people without autoimmune disease, the body gets rid of these self-reactive B cells via apoptosis, or programmed cell death. But "elevated levels of the molecule," the researchers said in a statement, "allow self-reactive B cells to escape from the bone marrow into the bloodstream and attack the body's own tissues."

"This is a good target for future therapies," said Changchun Xiao, a Scripps associate professor and co-senior author of the study, in the statement. "We now know that this is causative--it's not just a side effect." The study was published on Monday in Nature Immunology.

They figured it out by causing a virus to express certain microRNAs in stem cells that produce blood cells and platelets and then implanting them into mouse models. They found high levels of the microRNA miR-148a, which suppressed genes responsible for apoptosis, ultimately leading to the escape of self-reactive B cells.

Mice that expressed higher levels of MiR-148a developed lupus more quickly than their normal counterparts. Human lupus patients also overexpress MiR-148a, indicating a "pathway we might be able to regulate with a therapeutic," said David Nemazee, a Scripps professor and co-author of the study.

The next step, the team said, is to investigate MiR-148a's other effects in the body, to identify any side effects from inhibiting the molecule's function.

"Studies from other investigators have shown that miR-148a promotes the generation of plasma cells, a cell type responsible for generating antibodies in disease," Alicia Gonzalez-Martin, a Scripps research associate and the study's first author, told FierceBiotechResearch in an email. "This function might also contribute to autoimmune disease pathogenesis."

- here's the release
- read the journal abstract

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