Gene expression and response to DMTs

Hecker et al. Reassessment of blood gene expression markers for the prognosis of relapsing-remitting multiple sclerosis. PLoS One. 2011;6(12):e29648. Epub 2011 Dec 27.

Despite considerable advances in the treatment of MS, current drugs are only partially effective. Most MS’ers have reduced disease activity with therapy, but still experience relapses, increasing disability, and new brain lesions. Since there are no reliable clinical or biological markers of disease progression, long-term prognosis is difficult to predict for individual patients.

This study identified 18 studies that suggested genes expressed in blood as predictive biomarkers. The investigators validated the prognostic value of those genes in 148 MS’ers in total. Using these data, we tested whether the genes were significantly differentially expressed between MS’ers with good and poor courses of the disease. Poor progression was defined by relapses and/or increase of disability during a two-year follow-up, independent of the administered therapy. Of 110 genes that have been proposed as predictive biomarkers, most could not be confirmed in our analysis. However, the G protein-coupled membrane receptor GPR3 was expressed at significantly lower levels in patients with poor disease progression in all data sets. GPR3 has therefore a high potential to be a biomarker for predicting future disease activity.

This is what a gene expression profile looks like using an array chip. Each dot is a different gene. The colour coding informs you about the relative level of expression compared to control conditions.

“The holy grail in MS is to find prognostic markers that predict responses to treatment or disease course. This study is too small to give me any confidence, and will need to be reproduced in a larger number of MS’ers on DMTs.”

“If you were on a DMT would you want to know how well you are likely to do in the longterm on this drug? It may help you make a decision about a treatment.”

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


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