Deciphering multiple sclerosis disease processes along the disease course

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

Disease modulatory therapies (DMTs) are highly effective in the initial inflammatory phase, but much less so in later progressive disease phases.

We have recently invested 8.6 MUSD in the largest real-world study of MS in a nationwide population-based material, providing a unique basis for advancing our knowledge how MS evolves from a first triggering event to late progressive stages.

We hypothesize that chronic infection of memory B cell clones with Epstein-Barr virus (EBV) drives the early inflammatory component of MS, and that innate immune mechanisms and accelerated aging explain progressive MS.

The first aim will be addressed using advanced immunophenotyping of our unique MS cohort with full B cell repletion following antiCD20 therapy and a treatment trial with antivirals (collaboration Bergen).

We will address the second aim with epidemiological techniques and large-scale soluble biomarker and brain imaging profiling (collaboration Oslo, Basel), supplemented with deep brain imaging and molecular cerebrospinal fluid characterization in smaller clinical materials. Our previous research has transformed treatment of MS in Sweden in a unique way.

With this 5-year program we will make considerable progress towards implementation of precision medicine and further improve long-term outcomes for those affected by MS.