A team of researchers from Oxford University have uncovered why a once-promising class of drugs do not help people with multiple sclerosis.

The team of researchers say that a genetic variant linked to MS means the drugs which work for patients with other autoimmune diseases will not work for them. Indeed, they found the drug could actually make the symptoms worse.

Writing in Nature, the study shows how a person’s genetic make-up could affect how they responded to treatment. The anti-TNFs drugs have positive effects on patients suffering from rheumatoid arthritis and inflammatory bowel disease, but they have not done so for patients with MS and until now, researchers were unsure why.

New research from researchers at Oxford University has found that a gene called TNFRSF1A could be what is hindering the effectiveness of the drug. The gene variation has been associated with the risk of developing MS in previous studies. The normal version of the protein sits on the surface of cells and binds the TNF signalling module, however, the team found that the variant caused the production of an altered, shortened version which “mops up” TNF, preventing it from triggering signals – essentially the same thing that TNF blocking drugs do.

This explains the results of a study conducted ten years ago, which found that the drugs make MS patients significantly worse and exacerbate the disease. Professor Lars Fugger of the Nuffield Department of Clinical Neurosciences, who led the work, said: “The hope has been that analyses of the whole human genome would lead to findings that are clinically relevant.

“We show that this is possible. It’s one of the first such examples, certainly in autoimmune disease.”

He added: ‘Whilst the TNFRSF1A gene variant is linked to a modest risk of developing MS, the drug that mimics the effect of the variant has a considerably greater impact.

“The effects of genetic variants influencing disease risk or resistance can be amplified by drugs. This has often been completely overlooked, but will be critical for using genetic findings in a medical context.”