Researchers Discover How New MS Drug Works

shutterstock_152357099But it A new type of drug called dimethyl fumarate was recently approved in Europe as a basic treatment for multiple sclerosis. Various clinical studies have shown that it is effective in treating the symptoms of the said disease. But the underlying mode of action is not entirely known. But now, scientists from Bad Nauheim’s Max Planck Institute for Heart and Lung Research and the University of Lubeck have finally discovered how it works in treating MS symptoms.

Multiple sclerosis is a disease of the central nervous system that affects the nerve fibers in the brain and the spinal cord. It causes damage to the protective myelin sheath in the nerve cells, which affects how signals are transmitted and received within the CNS. The disease has no cure so far and its cause still remains unknown. The current treatments available help treat the symptoms to make MS patients able to manage living with the disease.

The basic treatment for MS usually involves beta interferons and glaitiramer acetate. Both treatments require using injections under the skin or into the muscle, which can be quite a discomfort among MS patients. Dimethyl fumarate or DMF is different in that it can be taken in tablet form. And recent studies indicate that its effectiveness is comparable to that of current established treatments.

DMF has been used for almost 20 years for treating psoriasis. But scientists know little of how it works on the immune function. Scientists from the team of Markus Schwaninger of the Institute of Experimental and Clinical Pharmacology and Toxicology at the University of Lubeck, and Nina Wettschureck’s research groups at the Max Planck Institute for Heart and Lung Research in Bad Nauheim have found out just how the compound works.

The researchers used a standardized mouse model of MS where drugs trigger an autoimmune response, leading to characteristic symptoms within a matter of days. This way, the researchers were able to induce certain symptoms comparable to those observed in patients with MS. According to Wettschureck, “In the group we treated with DMF, the problems with motor function were considerably lower than in the control group.”

The researchers were able to determine the compound’s mode of action by treating genetically modified mice the same way. Schwaninger explained, “In mice that don’t have the gene for the receptor called HCA2, DMF was unable to prevent the signs of paralysis.” This indicates that the HCA2 receptor plays a big role in the therapeutic effect of DMF in MS.

The HCA2 receptor is a so-called G protein-coupled membrane receptor which can be found in certain types of white blood cells called neutrophil granulocytes. “In animals treated with DMF, the number of granulocytes that infiltrated the nervous system was much lower than in untreated animals. In animals without the HCA2 receptor, the number of invasive granulocytes remained equally high despite treatment with DMF,” Wettschureck added.

Other cell culture experiments also showed that the activation of the HCA2 receptor causes the infiltration of white blood cells into the central nervous system. DMF blocks this infiltration, which results in the prevention of inflammation “Our study has enabled us to provide the first evidence that DMF’s protective effect is due to the HCA2 receptor. However, we are not ruling out the possibility that there may also be other mechanisms,” Wettschureck further added.

The researchers are hoping that this discovery will aid in the development of a wider range of treatments for MS.

Source: Max-Planck-Gesellschaft. “Mode of action of new multiple sclerosis drug discovered.” ScienceDaily. ScienceDaily, 1 April 2014. www.sciencedaily.com/releases/2014/04/140401173136.htm

 
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