Future therapies for progressive multiple sclerosis

Abstract

The vast majority of interested clinicians or scientists, patients with multiple sclerosis, and carers would, surely, offer the absence of any useful disease-modifying treatments for progressive multiple sclerosis as one of the most important remaining challenges in relation to multiple sclerosis. As the foregoing has emphasized, symptomatic approaches and therapies for progressive MS have made an enormous aspect on many of the major problems commonly associated with longstanding disease, perhaps particularly incontinence, pain, spasticity, and mood disturbance. Also and arguably even more dramatically, there has been a sea change in our ability to prevent relapses in MS over the past three decades - from no useful treatments at all, to half a dozen licensed (or likely soon-to-be-licensed) relapse-reducing agents, including monoclonal antibodies capable of preventing up to 80% relapses. Many were surprised if not shocked that the therapeutic ability to stop relapses does not bring with it a comparable impact on disease progression, but one major effect of the numerous, large-scale, and high-quality trials of relapse-preventing immunotherapies for MS has been to inform our understanding of this disease, and to illustrate that the link between relapses and disability progression is not direct, and that successfully treating the first may have no effect on the second. The last decade has consequently seen a very serious reorientation of therapeutic research in MS, with the realization that the problems of progressive disability and its treatment, in both secondary and primary progressive disease, need to be addressed separately and distinctly from the problem of relapses. The question now is whether the next 30 years may see the same level of success in developing disease-modifying treatments for progressive MS as the last three decades have seen in therapies for relapsing-remitting disease. Some might argue that the omens are not good, and the problems rather greater - in the 1980s, there were a large number of prescribable drugs available that were at least capable of significantly suppressing or altering immune function, while at present, there are no drugs that can modify neuronal or axonal loss in any progressive neurodegenerative disorder. However, the pace and scale of therapeutic research in recent years, the extraordinary advances in stem cell science, and the remarkable changes in molecular medicine - but above all the single fact that at least we have identified and are attempting to address the right question, that of halting (or, better, reversing) progressive neurodegeneration in MS rather than focussing exclusively on inflammatory relapses; all this must surely give grounds for reasonable and realistic optimism.