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Researchers Uncover a Novel Mechanism of Action of a Potential New Drug for the Treatment of Multiple Sclerosis
October 12, 2006Virginia Commonwealth University researchers have identified a unique mechanism of action of a new drug that shows great promise for the treatment of multiple sclerosis.
The 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.
In this 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.
According 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the entire inflammatory pathway, possibly without the side-effects caused by medications such as Vioxx, that have been withdrawn from the pharmaceutical market.
FTY720, a 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.
"By clearly 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," said Spiegel.
This work was supported by grants from the National Institutes of Health, and the National Science Foundation.
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.
Virginia Commonwealth University
According 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.
FTY720, a 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.
"By clearly 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," said Spiegel.
This work was supported by grants from the National Institutes of Health, and the National Science Foundation.
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.
Virginia Commonwealth University
Multiple Sclerosis News and Current Multiple Sclerosis Events RSSTrapping white blood cells proves novel strategy against chronic viral infections
Seeing disease-fighting white blood cells vanish from the blood usually signals a weakened immune system. But preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection, researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found.
Trapping white blood cells proves novel strategy against chronic viral infections
Seeing disease-fighting white blood cells vanish from the blood usually signals a weakened immune system. But preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection, researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found.
Protein complementarity may offer new insights into autoimmune diseases
The discovery of "complementary" antibodies against plasminogen in patients with blood vessel inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCAs) may lead to new approaches to research, testing, and treatment of ANCA vasculitis and other autoimmune diseases, suggests a paper in the December Journal of the American Society of Nephrology (JASN).
UNC study: shape, not just size, impacts effectiveness of emerging nanomedicine therapies
In the budding field of nanotechnology, scientists already know that size does matter. But now, researchers at the University of North Carolina at Chapel Hill have shown that shape matters even more - a finding that could lead to new and more effective methods for treating cancer and other diseases, from diabetes and multiple sclerosis to arthritis and obesity.
Multiple Sclerosis: new MRI contrast medium enables early diagnosis in animal model
In an animal model of multiple sclerosis (MS), neuroradiologists and neurologists of the University hospitals of Heidelberg and Würzburg have been able to visualize inflammatory tissue damage, most of which had remained unrecognized up to now, with the aid of a new contrast medium, Gadofluorine M, in magnetic resonance imaging.
New Guidelines for Treating Rheumatoid Arthritis
Proven combinations of medicines and the introduction of new anti-arthritis drugs have significantly improved the treatment of rheumatoid arthritis (RA), according to guidelines issued by the American College of Rheumatology and co-authored by physicians at the University of Alabama at Birmingham (UAB).
Milestone for cannabinoid MS study
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study at the Peninsula Medical School in Plymouth has reached an important milestone with the news that the full cohort of 493 people with multiple sclerosis (MS) has been recruited to the study.
Statins have unexpected effect on pool of powerful brain cells
Cholesterol-lowering drugs known as statins have a profound effect on an elite group of cells important to brain health as we age, scientists at the University of Rochester Medical Center have found. The new findings shed light on a long-debated potential role for statins in the area of dementia.
Best treatment for MS may depend on disease subtype
Animal studies by University of Michigan scientists suggest that people who experience the same clinical signs of multiple sclerosis (MS) may have different forms of the disease that require different kinds of treatment.
Medicines derived from cannabis: a review of adverse events
Researchers at the McGill University Health Centre (MUHC), McGill University and the University of British Columbia (UBC) determined that medical use of cannabinoids do not cause an increase in serious adverse events, but are associated with an increase in some non-serious adverse events.
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