Multiple sclerosis; from disease mechanisms to optimized treatment

Multiple sclerosis (MS) features aberrant adaptive immune reaction towards central nervous system antigens leading to myelin and neuron/axon damage.

Highly effective disease modulatory treatments (DMTs) have transformed the outlook for newly diagnosed patients, but data on long-term DMT risk-benefits and pathogenic mechanisms in later progressive disease phases is still restricted.

This project focuses on three areas; (i) explore mode of action of B cell depleting DMTs to inform on pathogenic mechanisms in early MS using advanced immunophenotyping; (ii) use a nationwide drug trial (CombatMS) to address comparative risk-benefit with current MS DMTs using novel imaging and soluble biomarkers and; (iii) use experimental models and soluble/ imaging biomarker profiling to shed light on pathogenic mechanisms in later disease stages and to develop a trial design suitable for reparative therapeutic strategies.

Underlying hypothesizes for the study is that B cell-depleting therapies induce long term remission in RRMS with major risk-benefit advantages compared to other DMTs, but do not affect the brain intrinsic disease processes of later disease stages.

Characterization of novel imaging and soluble biomarker profiles reflecting these intrinsic processes is possible and a requisite to develop reparative strategies.

Collectively, results are likely to in the short-term help optimizing treatment algorithms for existing DMTs and facilitate development of reparative strategies long-term.