New MS Drug Target Shows Promise

By Jeffrey Perkel
HealthDay Reporter
Monday, February 18, 2008; 1:00 PM

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MONDAY, Feb. 18 (HealthDay News) -- A high-tech molecular fishing expedition has led researchers to two potential therapeutic targets for the treatment of multiple sclerosis.

The data implicate a pathway more typically associated with wound healing -- the blood clotting cascade -- than in the development of multiple sclerosis (MS).

"There is no coagulation component to MS," explained Patricia O'Looney, vice president of biomedical research at the National Multiple Sclerosis Society.

But coagulation factors also play a role in inflammation, which is a component of the disease, she noted.

"If you can use this pathway and engineer some new drug therapy that will turn on the anti-inflammatory pathway, that could benefit people with MS," O'Looney concluded. "So, this perhaps reveals new therapeutic targets."

The research was published Feb. 17 in the advance online edition of Nature.

In the study, a team led by Dr. Lawrence Steinman of Stanford University School of Medicine grouped MS brain lesions from six autopsied human subjects into three classes based on histological criteria. They then probed those samples, along with samples from two healthy controls, using a technique called mass spectrometry, which essentially identifies the proteins in a tissue based on their mass.

The result was a "proteome" -- a sort of protein index of the tissues. Of the 2,574 proteins the team identified from all the samples, they found a few hundred that were unique to MS. More than half of those proteins were of unknown function, but five were known players in blood coagulation -- a pathway not previously recognized as being involved in the origin and development of the disease. All five were found in a single type of lesion, called a "chronic active plaque."

Puzzled by that observation, Steinman's team then tested whether drugs that targeted two of the five coagulation pathway members, called tissue factor and protein C inhibitor, could alleviate the symptoms of MS in a mouse model of the disease.