Oral therapy may soon be possible with compounds protecting nervous system from MS damage
A new study has revealed that a newly characterized group of pharmacological compounds block both the inflammation and nerve cell damage seen in mouse models of multiple sclerosis (MS).
Washington: A new study has revealed that a newly characterized group of pharmacological compounds block both the inflammation and nerve cell damage seen in mouse models of multiple sclerosis (MS).
Lead author Jeffery Haines at the Icahn School of Medicine at Mount Sinai said that 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.
Haines added that 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.
The molecule that shuttles proteins between the nucleus and cytoplasm, XPO1 (also called CRM1,) 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, thereby reducing inflammation.
Mice showing hindlimb paralysis were able to regain motor function within two weeks after KPT-276 or KPT-350 were orally administered.
Patrizia Casaccia added that 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.
The study is published in the journal Nature Neuroscience.