Suppressing immunity in advancing MS

Although no direct evidence exists that the immune system per se initiates the attack on myelin in patients with multiple sclerosis (MS), several observations strongly support this theory. Immune infiltrates are present at the sites of greatest damage; animal models (e.g., experimental autoimmune encephalomyelitis) prove that T cells alone can transfer disease from affected to unaffected animals; and therapies that are aimed at either modulating or suppressing the immune system can reduce disease activity. Pathologically, the destructive process includes not only demyelination, but also the early loss of axons and neurons. It is not known how inflammation leads to loss of neuronal elements but once this loss begins, it becomes a neurodegenerative condition—and may be the ultimate cause of clinical impairment and disability in MS. The effectiveness of a treatment may be dependent on which of the intertwined pathologic processes of immune-mediated inflammation and neurodegeneration predominates in the patient. In some patients, the destructive process ultimately leading to irreversible neurodegeneration arises early, becoming extensive and disabling. More powerful immunosuppression may be warranted in this select group of patients; however, because of the toxicity of these agents, they are often reserved until more advanced disabilities are present, a time when destruction may already be irreversible. It is not …