b'and no new MRI lesions but is still seeinglab for CAR-T therapy. One of the CAR-T targets progression of disability. Although pastwould be the B-cell follicles in the CNS. research has focused on relapses, PIRA mayDbe the major driver of disability in MS. TheDeeccoonnddiittiioonniinnggaannddlloossssonumber of relapses that a person has in theiroffnneeuurraallrreesseerrvveersttwoyearsafterdiagnosisdoeshavePIRA may also be driven by loss of neural some predictive value for future disability.reserve. This means the CNS loses its ability More relapses in those rst two years are linkedto adapt to prior injuries, such as MS lesions, to a higher chance of walking issues in theas we age. In this case, worsening disability future. After those rst two years, however,may not be due to ongoing inammation as most disability in MS seems to be driven bymuch as the normal aging process. We hope PIRA.that neural repair, or neural plasticity, will be F theanswertostoppingandreversingMS Frroommffoorreessttrreettoogglloowwiinnggeemmbbeerrss disability in this situation.There are likely several potential explanationsAll of us may lose some abilities if we are for PIRA. These include smoldering inammation,deconditioned. This is especially true for those loss of neural reserve, and deconditioningliving with MS. Weve come a long way from because of a lack of exercise.the days when people with MS were discouraged Lets start with smoldering inammation.from exercising for fear that it would worsen This is low-level inammation that causes slowtheirfatigue.Exercise,rehabilitation,and progression of disability and slowly enlargingwellness are essential tools for slowing and lesions on brain MRI. The obvious inammationadapting to disability. Physical therapists and seen with MS that causes relapses and newexperienced exercise trainers can help you inammatory MRI lesions could be compareddesign a program to help achieve your tness to a raging forest re. Smoldering inammationgoals. and the associated slow disability progressionOur understanding of immunopathology might be compared to glowing embers rathercontinues to grow, and hopefully, it will move than a raging re. us one step closer to an MS cure. We know This subtle inammation may be driven bymuch more today about MS than we did in cells in the immune system called microgliathe past. While the human immune system is and the B cell follicles in the CNS, which wedauntingly complex, these same complexities mentioned earlier. Smoldering inammationoffer the potential for many future therapeutic may be present early in MS and may persistapproaches. throughout a persons life. Our current DMTs are effective at quieting the big forest re butCOOLING VESTS may be less effective at stopping smolderingYOU WANT inammation. TO WEAR.WeanticipateFDAapprovalofanoral medication, tolebrutinib, later this year. This BTK inhibitor (Bruton tyrosine kinase) will be approved for secondary progressive without activity. This form of MS is primarily drivenMSF cooling program supplierbysmolderinginammation.Researchers855-232-7233are also looking at engineering T cells in the 17 msfocusmagazine.org'