Inflammatory Cells Halted in Mouse Models of Multiple Sclerosis

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Mouse models of multiple sclerosis were able to halt disease progression after targeting the nucleus of inflammatory cells.

Pharmacological compounds have the ability to block the inflammation and nerve cell damage that occurs in multiple sclerosis (MS), according to research published online in Nature Neuroscience.

Researchers from the Mount Sinai Hospital and the Mount Sinai School of Medicine observed mouse models of MS to determine whether pharmacological compounds that were designed to block the function of the molecule that gives passage between to proteins between the nucleus and the cytoplasm (called XPO1 and CRM1) could halt the disease progression.

Prior research conducted at Mount Sinai has indicated that XPO1 and CRM1 abilities are altered in neurodegenerative diseases, such as MS and other diseases.

The researchers found 2 chemical agents called KPT 276 and KPT 250 inhibited XPO1 and CRM1 from removing the proteins out of the nucleus of the nerve cells in the mouse models. This protected the cells from free radicals and structural damage, the authors said. The compounds additionally were able to prevent the inflammatory cells from multiplying, which, in turn, reduced inflammation.

“The compounds identified in this study, when administered orally, both reduced the inflammation that is a hallmark of MS and protected against the nerve cell damage seen in mouse models of the disease," the study’s lead author Jeffery Haines, PhD said in a press release. “The MS 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.”

The mice which demonstrated hind limb paralysis additionally regained motor function within 2 weeks after oral administration of either KPT 276 or KPT 350. The authors believe that the treatment options for neurodegenerative disorders, such as MS, amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, can be improved based upon these findings by targeting nuclear transport.

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

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