Multiple Sclerosis Gene Variant Role Discovered

Multiple Sclerosis Gene Variant Role Discovered

Researchers at Oxford University have identified the role of a gene variant in multiple sclerosis. The study was led by a team from Oxford University, along with German, Danish and U.S. colleagues, and published in the journal Nature.

The discovery emerged by analyzing the human genome. Researchers have focused mainly on the analysis of TNFRSF1A variant gene, a  gene associated with multiple sclerosis development. After molecular analysis, researchers were able to demonstrate that this gene variant causes a short form of the TNFR1 protein. TNFR1, or p55 or the CD120 is the receptor for TNF alpha and TNF beta. After binding of TNF alpha to TNFR1 apoptosis is triggered, ie programmed cell death. Shortened form of this protein does not allow binding of TNF alpha. Medications used to treat autoimmune diseases,  inflammatory bowel disease and rheumatoid arthritishave the same mechanism of action. These drugs, monoclonal antibodies such as Infliximab, Adalimumab and Etanercept, prevents TNF alpha-receptor binding. Although these drugs are effective in treating autoimmune diseases, the researchers found no explanation why MS does not respond to such treatment.Dr Calliope Dendrou, one of the joint first authors of the paper from the Nuffield Department of Clinical Neurosciences at Oxford University, said: ” ‘Had we known this prior to the clinical trial of TNF blockers in MS patients, this could have helped to predict the poor outcome.”

Multiple Sclerosis

Professor Lars Fugger of the Nuffield Department of Clinical Neurosciences at Oxford University, said that it is extremely important to understand the biological details of a gene variant. Once these details understood, researchers can figure out which patients respond to treatment and who not. Also, Professor Lars Fugger also said that while TNFRSF1A gene variant is associated with a moderate risk of developing multiple sclerosis, drugs that mimic the effect of the variant gene have a  much higher impact.

Multiple sclerosis is a chronic autoimmune inflammatory disease of the central nervous system. Multiple sclerosis  is more common in young people, especially women, and it evolves with neural multifocal demyelination and the appearance of plaques of MS. It is a condition that develops gradually with periods of flares and periods of calm. MS patients have visual disturbances, sensory disturbances (paresthesia), motor disorders (paresis), progressive muscular atrophy, etc.. Also it can occur cerebellar disorders such as ataxia, impaired balance and coordination (intentional shaking). Other symptoms may be linked to speech: MS patients may have dysarthria, slow speech. Symptoms may even  go to seizures when sclerosis plaques  affects the cortex. MS is not curable, there is only symptomatic treatment.