June 27, 2014

Breakthrough in the Search for New Treatments for MS

Researchers at the University of Nottingham have discovered a molecular mechanism that encourages the body to produce its own beta-interferon. Some current disease-modifying treatments for relapsing forms of MS provide beta-interferon by injection. This discovery suggests that there might be a way of prompting the body to produce interferon, rather than having to introduce it through injection and could advance the development of new therapeutics for the treatment of MS. [Downer EJ, Clifford E, Gran B, Nel HJ, Fallon PG, Moynagh PN. J Biol Chem. 2011 Mar 25;286(12):10316-28. Epub 2011 Jan 18.]

Dr. Bruno Gran, Clinical Associate Professor in the Division of Clinical Neurology in the School of Clinical Sciences, and Professor Paul Moynagh from the National University of Ireland discovered a synthetic cannabinoid compound known as
R(+)WIN55,212-2. Cannabinoids are typically used to manage inflammatory conditions such as MS, arthritis and glaucoma.  Despite their growing clinical use, the exact mechanism is still not fully understood. Dr. Gran et al have demonstrated that R(+)WIN55,212-2 is unique in that it inhibits the pro-inflammatory signals produced by the immune system in MS, and at the same time, stimulates the body to produce interferon-beta, the anti-inflammatory molecule commonly used to treat MS.

Combined, these effects caused a significant reduction in the severity of disease in the animal model that mimics MS (EAE). Dr. Gran and colleagues also discovered that cells of the immune system obtained from the blood of people with MS are more sensitive to the effects of this drug than those obtained from people who do not have MS.

Under laboratory conditions, Drs. Gran and Moynagh found a way to encourage the body of the animal model to produce its own interferon-beta. Other experimental substances that have been tested in the laboratory to achieve the same effect generally cause the immune system to produce a mixture of anti-inflammatory and pro-inflammatory molecules, reducing overall efficacy. The predominantly anti-inflammatory effects of R(+)WIN55,212-2 appear promising for further research.

Interferons were first approved in Canada in 1995 and continue to represent one of the first line treatments for relapsing-remitting multiple sclerosis to slow the progression of disability, decrease the frequency of MS attacks, and reduce the number and volume of brain lesions seen on MRI. In Canada there are seven approved MS disease modifying therapies, four of which include beta-interferons:  Avonex®, Betaseron®, Extavia® and Rebif®. The other three therapies approved for treatment in Canada include glatiramer acetate (Copaxone®), natalizumab (Tysabri®) and fingolimod (Gilenya™).