b'Medicine and ResearchAAnnEEvvoolluuttiioonnooffTThhoouugghhttoonnWWhhaattDDrriivveessMMSSFFooccuusssshhiiffttssttootthheeeexxaammiinnaattiioonnoofftthheerroolleeooffBBcceellllss,,PPIIRRAABy Dr. Ben ThrowerMultiple sclerosis results from a complex(Briumvi). These B cell therapies represent interaction between genetic and environmentaloneofthemosteffectiveclassesofMS risk factors. Our understanding of how thesedisease-modifying therapies. factors lead to immune dysregulation continuesPPiivvoottiinnggffrroommrreellaappsseessttooPPIIRRAAto grow. MS was previously thought to onlyTraditionally, we have divided MS into several damage myelin. In 1998, Dr. Bruce Trapp andcategories: relapsing remitting, secondary his team showed us axons were also beingprogressive, and primary progressive. We attackedandtransected.Inthepastfewnow divide secondary progressive MS further: years, there have been other signicant shiftswith activity (meaning there are still clinical in how we think about the immunopathologyrelapses or new inammatory MRI lesions) of MS.and without activity (no relapses or new MRI P lesions).Piivvoottiinnggffrroomm T toT to BBcceellllssWeve seen the focus move from T cells asAlong with these classifications, it was the major driver of MS to realizing B cells alsobelieved that relapsing MS involved periods play a crucial role. The traditional animal modelof worsened inammation, which were linked used in MS research is the mouse experimentalto clinical relapses or new lesions on MRI. allergic encephalomyelitis model, a T cell-drivenThese were followed by periods of remissions, immune response. during which no relapses or new MRI lesions The realization that B cells play a signicantappeared. Over time, it was thought that role in human MS could mean we need aninammation became less pronounced, and animal model that better reects MS. B cellsMS transitioned into a secondary progressive may contribute to the immunopathology of MSphase. Primary progressive MS was characterized through antibody production, T cell activation,by the progression of disability from the onset. and the production of inammatory cytokines.In addition to this traditional understanding Over time, MS may result in B cells settingof MS, there was also a focus on relapses and up shop in the CNS via B cell follicles. We willnew lesions on MRI as outcomes in clinical come back to this later. trials.With the focus on the role of B cells in MS,Research is now showing there are problems we have also seen the development of B cellwith this view. Newer thinking is emphasizing therapiesincludingrituximab(Rituxan,the progression of disability independent of Truxima, and Ruxience), ocrelizumab (Ocrevus),relapse activity. PIRA refers to an individual ofatumumab(Kesimpta)andublituximabliving with MS who has had no recent relapses msfocusmagazine.org 16'