Drug Target for Progressive Multiple Sclerosis Discovered

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Inhibiting cytokines could prevent disease progression among those with multiple sclerosis.

Researchers have discovered how 2 cytokines may play a role in the development of progressive multiple sclerosis (MS). The findings, published by the Proceedings of the National Academy of Sciences, may form the foundation of a new treatment to prevent a more severe form of the condition.

In the study, the authors discovered that macrophage migration inhibitory factor (MIF) and the related protein, D-dopachrome tautomerase (D-DT), were linked to progressive MS. These cytokines are involved with cell communication and movement, according to the authors. The authors believe that the cytokines induce disease progression by increasing inflammation of the central nervous system.

Additionally, increased expression of MIF with a gene variant was found in patients with progressive MS, especially among men, according to the study.

These findings suggest that a genetic test could identify patients at risk of severe MS. The authors note that a more targeted therapy could be used as a precision medicine approach for patients with the MIF gene-related risk.

"The value of this discovery to patients is that there are now approved therapies, as well as new ones in development in the Oregon and Yale labs, which target the MIF pathway and could be directed toward progressive MS," said co-senior author Richard Bucala, MD.

A simple test to determine patients who may benefit from MIF inhibitors would escalate drug development while also reducing cost, risks of toxicity, and providing a targeted therapy, according to the study.

The authors discovered the cytokines by observing patients with MS and through immunologic and DNA analysis, according to the study.

The investigators also conducted cell studies. They found that a compound developed to treat MS-like disease in rodents effectively blocked the action of MIF and D-DT, which was the first time this was achieved, according to the study.

The authors believe that blocking the mechanisms of these 2 cytokines may prevent disease progression in humans, offering a preventive treatment for those at risk of severe MS.

MS affects more than 2.3 million individuals around the world. Without early intervention with effective therapies, these patients are at risk of severe disability and poor health outcomes.

"If you start a therapy before the disease has progressed very far, you have a much better opportunity to slow it or stop it," said co-senior author Arthur Vandenbark, PhD. "We now have a rational, molecular target for slowing or preventing the transition from relapsing-remitting to progressive MS, a stage of MS which is much more severe."

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