Australian researchers propose new hypothesis for MS

Australian authors describe a new 'paradigm' for the pathology of MS whereby oligodendrocyte apoptosis, and not a primary autoimmune process, triggers the cascade of events that leads to lesion development.Writing in Current Opinion in Neurology, Drs Michael Barnett and Ian Sutton describe recent observations in early MS lesions that have helped elucidate the events that occur before active demyelination. The observations challenge the traditional hypothesis that a primary autoimmune response specifically targeting myelin antigens is responsible for the development of MS.The authors say, "These observations suggest a novel paradigm of MS pathology, namely that oligodendrocyte apoptosis, in the absence of contact-dependent cell-mediate immunity, precedes myelin phagocytosis in the newly forming lesion." They propose that this apoptosis triggers the transformation of microglia into macrophages, which act in a scavenger capacity. The process, which takes place over hours to days, is followed by activation of a systemic immune response and subsequent increased tissue damage.The authors also suggest that the second, late phase of the disease involves a 'compartmentalisation' of the inflammatory response, which is largely isolated from systemic influence. This process is suggested to be the result of a gradual transition that occurs over months to years. The authors explain, "Pathological studies show different patterns of chemokine expression in acute and chronic lesions and while early relapsing MS is associated with recruitment of systemically derived immune cell populations, inflammatory responses in the late progressive phase appear to be locally regulated or 'compartmentalized.'" Inflammatory activity in this late phase is usually restricted to around the pre-existing lesions and rarely results in the development of new lesions, the authors note.The authors explain that the CNS is increasingly being recognised as a unique immune environment, and this compartmentalisation of the immune response may provide some explanation for the lack of efficacy of immunomodulatory and immunosuppressive therapies in late MS. They suggest that treatments aimed at this phase of the disease should therefore target resident CNS inflammatory cell populations, promote remyelination, and provide neuroprotection.Reference...