A newly characterized group of pharmacological compounds, when administered orally, blocks both the inflammation and nerve cell damage seen in mouse models of multiple sclerosis (MS), revealed a study published in the journal Nature Neuroscience.
Lead author Jeffery Haines at the Icahn School of Medicine at Mount Sinai said, "The multiple sclerosis drugs currently on the market and being tested elsewhere seek to reduce the immune attack on cells, but none of them 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."
AdvertisementXPO1 (also called CRM1), the molecule that shuttles proteins between the nucleus and cytoplasm, has been implicated in multiple sclerosis and a number of other diseases. Researchers found that two chemical agents, called KPT-276 and KPT-350, prevented XPO1/CRM1 from shuttling cargo out of the nucleus of nerve cells, which protected them from free radicals and structural damage. The compounds also stopped inflammatory cells from multiplying, thus reducing inflammation. During the study, mice showing hindlimb paralysis were able to regain motor function within two weeks after KPT-276 or KPT-350 were orally administered.
Patrizia Casaccia said, "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. Because traffic of molecules between the nucleus and the cytoplasm of nerve cells is altered in several other neurodegenerative disorders, targeting nuclear transport may have broader therapeutic implications in diseases like amyotrophic lateral sclerosis (ALS) and Alzheimer's disease."
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