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Deactivating protein may protect nerve fibers in MS

PORTLAND, Ore. Oregon Health & Science University neuroscientists are eyeing a protein as a potential therapeutic target for multiple sclerosis because de-activating it protects nerve fibers from damage.

OHSU researchers, working with colleagues at the Portland Veterans Affairs Medical Center and the University of Padova in Italy, have shown that genetically inactivating a protein called cyclophilin D can protect nerve fibers in a mouse model of multiple sclerosis. Cyclophin D is a key regulator of molecular processes in the nerve cell's powerhouse, the mitochondrion, and can participate in nerve fiber death. Inactivating cyclophilin D strengthens the mitochondrion, helping to protect nerve fibers from injury. The findings are published today in Proceedings of the National Academy of Sciences.

"We're extremely excited," said Michael Forte, Ph.D., senior scientist at the Vollum Institute at OHSU and the study's lead author. "While we can't genetically inactivate cyclophilin D in people, there are drugs out there that can block the protein. Our research predicts that drugs that block cyclophilin D should protect nerve fibers from damage in MS."

Such a drug would be the first therapy specifically for secondary-progressive MS, one of the more debilitating forms of MS involving an initial period of relapsing and remitting, followed by a steady worsening of symptoms. It affects half of the estimated 2 million people with MS.

The only available therapies for MS are anti-inflammatory drugs, which reduce the inflammation believed to spur certain T-cells in the body to attack myelin, the fatty sheath insulating nerve fibers in the brain and spinal cord. The fibers can't conduct impulses, leading to paralysis, memory loss, dizziness, fatigue, pain and imbalance. Over time, the nerve fibers themselves degenerate, leading to permanent functional deficits.

"All MS drugs available right now are anti-inflammatory," said study co
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
23-Apr-2007


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