Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system that affects more than two million individuals worldwide. MS begins with a relapsing-remitting (RR) course, while about 30% of the patients may advance to progressive MS (PMS), even with the treatment of high-efficacy disease modifying therapies (DMT). It is believed that RRMS and secondary PMS is the same disease continuum without an distinct boundary. But this way of classification has several limitation: (1) it cannot explain why some patients remain a RR course for years, while a subset of patients develop to progressive phase rapidly; (2) patients with certain characteristics (e.g. male gender, older age at onset) are inclined to have a PMS transition; (3) patients with PMS show worse response to B-cell depleting therapies than RRMS.
The aim of this 3-year project is to interrogate unique UK Biobank MS cohort with novel analytical approaches to revisit the phenotype of MS. We hypothesize that (1) PMS is a separate disease from RRMS, rather than the same disease continuum with an indistinct boundary; some patietns may be destined to develop a progression course at the onset of disease. (2) Both genetic and immune factors may decide whether a patient is going to develop progressive disease course or remain RR course. Our original point of view and validation will provide new insights to the mechanism of MS and help guding personalized treatment for MS.
