Oxford researchers solve MS drug mystery

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A study by a team of Oxford scientists has solved a decade-long medical puzzle explaining why drugs prescribed for people suffering from Multiple Sclerosis (MS) often made their symptoms worse. 

Researchers were unsure why the drugs used successfully on other autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease did not work for patients with MS.

For the past three years the Oxford University team, in collaboration with German, Danish and US scientists, has focused on one particular variant gene called TNFRSD1A, which was previously associated with the risk of developing MS. 

The normal gene is responsible for the production of a protein which sits on the surface of cells and binds TNF, an important signalling molecule involved in a number of biological pathways in the body. 

The Oxford-led research team discovered that the variant caused the production of an altered, shortened version of the protein which mops up TNF, preventing it from signalling. 

According to the joint authors of the paper, Mr Adam Gregory and Dr Calliope Dendrou, from the Nuffield Department of Clinical Neurosciences, “the drugs given to MS patients [TNF blockers] mirror the action of the variant gene, thereby promoting or exacerbating their symptoms.”

On its own, the genetic variant TNFRSD1A is linked only to a modest risk of developing MS. However, in conjunction with the drugs its effect is greatly amplified.

According to the authors of the study, it is “the first of its kind” and demonstrates the clinical relevance of studying genetics. 

“A prior knowledge of the functional effects of the gene variant could have helped predict the poor outcome of the drugs,” explained Mr Gregory and Dr Dendrou. The study shows how an understanding of the overall mechanisms that lead to disease through genetics can ensure better drug administration. 

Mr Gregory and Dr Dendrou told Cherwell, “we’re delighted to have been part of what we believe is a very important study, and that this has been reflected in the media interest that we’ve had since its publication.”

Multiple sclerosis (MS) is a neurological condition which affects around 100,000 people in the UK. In MS, the coating around nerve fibres called myelin is damaged by the immune system which mistakes it for a foreign body and attacks it. This damage disrupts messages travelling along the nerve fibres between the brain and the body; they can slow down, become distorted, or not get through at all.

Nick Rijke, Director of Policy and Research at the MS Society, commented, “There are many genes associated with MS, but we know little about the role they play or the influence they have on the condition. This important study has shown that some of your genes can play a part in deciding whether or not you respond to a treatment.  In the future this could help ensure that people with MS are offered drug treatments that are most likely to work for them.”

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