Is remyelination a reasonable target in PMS?

The development of immunotherapies has led to major therapeutic progress in MS, with a robust impact on relapse rate. Concerning their influence on disability accrual, several long-term observational studies have suggested a reduced risk of decline in neurologic function in patients with relapsing-remitting MS. In the progressive forms of the disease, few trials with immunosuppressants have shown some relatively minor effect on progression of handicap. Irreversible neuronal/axonal damage and loss accounts for handicap progression, and takes place early in disease evolution, i.e. not only during the progressive phase, but also in the remitting phase. In this context, promoting remyelination, which results in prevention of neurodegeneration, represents a promising strategy to slow or suppress disability progression. Whether these remyelination strategies should be proposed to patients with progressive disease remains uncertain, with the risk of trial failure due to existing severe disability and neuronal damage. This is why most trials to date have included patients with RMS (MS with relapses, with either a relapsing-remitting or a progressive phenotype. To date, the few completed phase 2 trials have not demonstrated clinical impact, but some showed efficacy on imaging outcomes. Other trials included patients with optic neuritis, with some positive results on VEP latency. Even if a solid conclusion from these trials is premature, and with the lack of evidence that these stratégies can be extrapolated to progressive MS, these very recent results, suggesting that it might be possible through remyelination to prevent neurodegeneration, open exciting perspectives for prevention of disability progression in MS.