Prediction of multiple sclerosis response to treatment
MS is a devastating disease of the central nervous system that mainly affects young adults. Disease pathogenesis relates to an immune-mediated destruction of myelinated central nerve fibres leading to the deterioration of neurological functions. Over the last 10 years, various biotherapies have become available with a significant impact on disease relapse rate. Treatment with first line therapies such as interferon-β or copolymer acetate is not always successful and patients switch to second line therapies such as natalizumab (NTZ). However, NTZ carries an increased risk of herpes infection, progressive multifocal leukoencephalopathy (PML) and even acute leukaemia. The EU-funded BEST MS (Best escalation treatment in multiple sclerosis (MS)) project wished to evaluate the best benefit to risk ratio of NTZ treatment. They focused on obtaining the best composite criteria of response to NTZ during the first year of treatment to predict disease activity in the next years of treatment as well as any serious adverse events in particular PML. Researchers performed a retrospective analysis of samples collected from 1 500 NTZ-treated patients stratified as responders and non-responders. Thirty of these patients had developed PML. Researchers applied metabolomics, genomics, diverse cellular assays, and metagenomics to identify biological markers that could predict the response to NTZ. They identified genes associated with non-response to NTZ, while some others such as MMP9 offered an interesting biomarker for prediction of progressive multifocal leukoencephalopathy. Furthermore, the project confirmed the use of a prediction test for progressive multifocal leukoencephalopathy that measures the levels of L-selectin (CD62L). Overall, the project proposed monitoring the risk of developing PML at the individual level, providing a paradigm for precision medicine in neurodegenerative disease. Although the concept of personalised medicine is not new, powerful methods and novel technologies are required to guide evidence-based clinical practice. BEST MS partners envision a response prediction test that will allow physicians to choose among the 15 biological drugs available for MS treatment.
Keywords
Multiple sclerosis, natalizumab, progressive multifocal leukoencephalopathy, BEST MS, L-selectin
