Experimental Drug Prevents Multiple Sclerosis in Animal Model

Researchers have shown that an experimental drug (the synthetic cannabinoid known as R(+)WIN55,212-2) caused significant reduction in the severity of an animal model of multiple sclerosis (MS).

The drug had previously been shown to reduce symptoms in other inflammatory diseases such as Alzheimer’s disease. In the current study, investigators at the University of Nottingham (United Kingdom) and their collaborators at the National University of Ireland (Maynooth) used the drug to treat an animal model of MS.

They reported in the March 25, 2011, issue of the Journal of Biological Chemistry that R(+)WIN55,212-2 blocked the proinflammatory signals produced by the immune system in MS. At the same time, the drug stimulated production of interferon-beta, an anti-inflammatory molecule that is commonly administered to patients to ameliorate symptoms of MS.

The investigators demonstrated that at the molecular level R(+)WIN55,212-2 was a novel regulator of TLR3 (Toll-like receptor-3) and TLR4 (Toll-like receptor-4) signaling by inhibiting the proinflammatory signaling axis triggered by TLR3 and TLR4, whereas selectively augmenting TLR3-induced activation of interferon regulatory factor 3 (IRF3) and expression of interferon-beta. R(+)WIN55,212-2 also induced interferon-beta expression in MS patient peripheral blood mononuclear cells, which suppressed inflammatory signaling in these cells.

Contributing author Dr. Bruno Gran, associate professor of clinical neurology at the University of Nottingham, said, “Under laboratory conditions we have found a way of encouraging the body to produce its own interferon-beta. When other experimental substances have been tested in the laboratory to achieve this effect, they usually cause the immune system to produce a mixture of anti-inflammatory as well as proinflammatory molecules, typically reducing the overall efficacy. In the case of the compound tested in this study, the predominantly anti-inflammatory effects appear promising for further preclinical, and hopefully clinical, testing.”

Related Links:
University of Nottingham
National University of Ireland