New Compounds Protect Against Nervous System Structural Damage from Multiple Sclerosis

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Newly characterized compounds found to block inflammation and nerve cell damage.

Newly characterized compounds found to block inflammation and nerve cell damage.

A group of pharmacological compounds was found to block inflammation and nerve cell damage in mouse models of multiple sclerosis (MS), a recent study found.

The study, published online in the journal Nature Neuroscience, noted that nerve cells become highly susceptible to damage after myelin is stripped from nerve fibers. This process leads to the gradual decline found in progressive forms of multiple sclerosis.

"The compounds identified in this study, when administered orally, both reduced the inflammation that is a hallmark of multiple sclerosis and protected against the nerve cell damage seen in mouse models of the disease," lead author Jeffery Haines, PhD, a said in a press release. "The multiple sclerosis drugs currently on the market and being tested elsewhere seek to reduce the immune attack on cells, but none target neurodegeneration nor do they work to restore nerve cell function. The findings of this new study represent an exciting step in the process of advancing new oral treatment options."

Prior research has found the trafficking of protein molecules between the nucleus and cytoplasm changes in neurodegenerative disease. The XPO1 (CRM1) molecule that traffics proteins between the nucleus and cytoplasm has been implicated in MS and several other diseases.

The current study evaluated whether pharmacological compounds that block the function of XPO1/CRM1 could halt the progression of the disease in mouse models that show some MS characteristics. Two chemical agents, called KPT-276 and KPT-350, stopped the XPO1/CRM1 molecule from transporting cargo out of the nucleus of nerve cells.

This was found to protect from free radicals and structural damage, in addition to stopping inflammatory cells from multiplying, which reduced inflammation. In mice whose hind limbs were paralyzed, motor function was regained within 2 weeks following orally administered KPT-276 or KPT-350.

"The study results elucidate the molecular mechanisms underlying disease progression in multiple sclerosis models, providing a basis for future clinical trials to determine safety and efficacy of these chemical agents in humans with demyelinating disorders," senior author Patrizia Casaccia, MD, PhD, said in a press release.

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