“The study below looks for predictive genetic response markers to IFN-beta and GA and suggests that variants in a particular immune receptor called CCR5 is predictive of a response to these DMTs. This receptor is very interesting biologically and is the one that is the co-receptor that HIV uses to infect cells. A particular variant in this receptor renders the carrier resistant to infection with HIV. It would be interesting to ask how is this receptor linked to a treatment response in MS?”
“It is becoming increasingly important to be able to identify who is going to be a responder or non-responder to IFN-beta or GA before starting treatment. This will allow us to screen individuals and offer them an effective 1st-line drug that is safe. This will allow us to select MS drugs so as not to expose too many MSers to risky therapies. If only it was this simple. Unfortunately, we don’t have any validated baseline response markers in clinical practice; we have some promising ones identified in the academic setting but none that have made it into the clinic. The only marker that has made it into the clinic is neutralizing anti-interferon beta antibodies or NABs. The earliest we can screen for these is at about 6 months. NABs only predict failure of therapy in the future and are not a positive predictor.”
Kulakova et ak. Comparative pharmacogenetics of multiple sclerosis: IFN-β versus glatiramer acetate. Pharmacogenomics. 2014 Apr;15(5):679-85.
Background: Various diseases require the selection of preferable treatment out of available alternatives. Multiple sclerosis (MS), an autoimmune inflammatory/neurodegenerative disease of the CNS, requires long-term medication with either specific disease-modifying therapy (DMT) – IFN-β or glatiramer acetate (GA) – which remain the only first-line DMTs in most countries. A significant share of MS patients are resistant to treatment with one or the other DMT; therefore, the earliest choice of preferable DMT is of particular importance. A number of conventional pharmacogenetic studies performed up to the present day have identified the treatment-sensitive genetic biomarkers that might be specific for the particular drug; however, the suitable biomarkers for selection of one or another first-line DMT are remained to be found. Comparative pharmacogenetic analysis may allow the identification of the discriminative genetic biomarkers, which may be more informative for an a priori DMT choice than those found in conventional pharmacogenetic studies.