Researchers uncover specific immune molecules that could act as biomarkers for more severe forms of multiple sclerosis. The findings might help to personalize treatments for those at most risk.

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New research adds another piece to the MS puzzle.

Multiple sclerosis (MS) is a chronic condition affecting the central nervous system, comprising the brain and spinal cord. Exactly why MS occurs is unknown, and treatment options are still limited.

Myelin is a waxy coating on nerves that is essential for the transmission of messages throughout the nervous system.

With MS, this myelin coating is degraded over time, slowing or entirely stopping signals from traveling along nerve fibers. This leads to problems with muscle weakness, coordination, and balance.

Symptoms vary significantly between individuals but tend to include difficulty walking, vision problems, tremor, fatigue, and depression.

MS is thought to be an autoimmune disease, although the reasons why the immune system turns on myelin are not yet understood. This is an unpredictable disease that ranges from relatively benign to disabling.

Most people with MS have the relapsing-remitting (RRMS) form, wherein attacks of symptoms, or relapses, occur from time to time. Between relapses, there can be months or years without any symptoms. Over half of those with RRMS will eventually move on to develop progressive MS, in which symptoms gradually get worse without extended recovery phases.

But some individuals do not experience the relapsing-remitting phase and instead go straight to progressive MS. This is known as primary progressive MS.

Recently, scientists from Yale University in New Haven, CT, Oregon Health & Science University in Portland, and the University of California set out to understand the molecular mechanisms involved in MS that dictate whether it begins slowly or leaps swiftly to the more severe form.

Their findings are published this week in the journal PNAS.

The researchers examined more than 100 people with MS and combined these clinical observations with an analysis of more than 500 DNA and plasma samples.

They found that two closely related molecules were associated with a swift progression to a more severe form of the disease. The molecules in question are cytokines – that is, a broad group of small proteins involved in cell signaling that are particularly important for immune function.

The specific cytokines are macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT). Both appear to increase inflammation and have been associated with the worsening of certain autoimmune diseases.

A gene variant known to occur more frequently in patients with the progressive form of the disease also occurred more frequently in people with increased MIF expression – in men, in particular.

The current findings are important as they might lead to a simple genetic test to ascertain which person’s disease is most likely to progress faster. And potentially, the sooner treatment starts, the more effective it could be.

As co-senior study author Dr. Richard Bucala explains, “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.”

If MIF blockers could be targeted to those who are in most need, the drug development would be accelerated by reducing cost, minimizing the risks of toxic effects, and providing a treatment genetically tailored to the patient.

As part of their investigation, the team used a drug that targets CD74 receptors, the binding site for both MIF and D-DT. They found that MS symptoms improved as MIF and D-DT activity was reduced.

The researchers are hopeful that these findings will help to improve MS treatments for those that need them most.

If you start a therapy before the disease has progressed very far, you have a much better opportunity to slow it or stop it. We now have a rational, molecular target for slowing or preventing the transition from [RRMS] to progressive MS, […] which is much more severe.”

Prof. Arthur Vandenbark, Oregon Health & Science University

The progression of MS and its molecular mechanisms still hold many mysteries. Researchers are gradually picking away at the knots. Each new finding is a step closer to better treatment and an eventual cure.