Researchers Uncover a Novel Mechanism of Action of a Potential New Drug for the Treatment of Multiple Sclerosis
Wednesday, Oct. 11, 2006
Virginia Commonwealth University researchers
have identified a unique mechanism of action of a new drug that shows great
promise for the treatment of multiple sclerosis.
researchers report the unique action of FTY720, or Fingolimod, an
immunosuppressant drug that was already known to affect the functioning of the
immune system by preventing the egress of white blood cells from the lymph
nodes into the blood. The article was pre-published as a First Edition Paper in
Blood, The Journal of the American Society of Hematology, which appeared online
on Sept. 28.
study, the research team observed that FTY720 also inhibited the activity of a
key enzyme called cPLA2, which is necessary for the production of inflammatory
mediators, known as eicosanoids. Eicosanoids drive inflammatory disorders such
as asthma and multiple sclerosis.
to Sarah Spiegel,
Ph.D., professor and chair in the VCU
Department of Biochemistry, and lead author on the study, the inhibition
of cPLA2 would shut down the entire inflammatory pathway, possibly
without the side-effects caused by medications such as Vioxx, that have been
withdrawn from the pharmaceutical market.
drug developed by Novartis, has shown considerable therapeutic effects in a
recent small, placebo-controlled clinical trial involving patients with
relapsing multiple sclerosis. The study was published in the September 2006
issue of the New England Journal of Medicine by an international research team.
With its novel mode of action and the added benefit of an oral formulation,
further clinical development of FTY720 might have a major impact on treatment
of MS, said Spiegel.
understanding the mechanism of action of drugs such as FTY720, we can develop more
optimal treatments for inflammatory disease such as asthma or MS. This drug may
prevent both inflammation and axonal damage, including demyelination, which are
characteristic of MS,"
This work was supported by grants from the National
Institutes of Health, and the National
The research team included Shawn G. Payne, Ph.D., a
researcher in the VCU Department of Biochemistry, who made the discovery of the
novel actions of this drug; researchers Carole A. Oskeritzian, Ph.D., Rachael
Griffiths, Preeti Subramanian, all in the VCU Department of Biochemistry;
Suzanne E. Barbour, Ph.D., and Charles E. Chalfant, Ph.D., both professors in
the VCU Department of Biochemistry who contributed vital reagents and expertise;
and Sheldon Milstien, Ph.D., a neuroscientist with the NIH.
About VCU and VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.