Emerging therapies in multiple sclerosis

Abstract

Multiple sclerosis (MS) is the most common neurological cause of disability in young people. The disease-modifying treatments, IFN-β and glatiramer acetate, have been widely available over the last decade and have shown a beneficial effect on relapse rate and magnetic resonance imaging parameters of disease activity; however, their effect on disease progression and disability is modest. Therefore, the search for alternative treatment strategies continues. As understanding of the heterogeneous pathophysiology of MS has increased, emphasis has shifted to more selective therapy that targets components of the inflammatory cascade and the promotion of remyelination and neuroprotection. These agents target the blood–brain barrier, systemic immune dysfunction, local inflammation and neurodegeneration. Combination therapies are being investigated for patients who fail first-line treatments. Many new drugs are being developed and tested that address these issues with the aim of finding a more effective and convenient therapy. These include humanised monoclonal antibodies such as daclizumab (IL-2 antagonist), oral immunomodulators such as sirolimus and statins and neuroprotective agents such as NMDA antagonists and Na⁺-channel blockers. Many of the treatments discussed in this review are still at early stages of development, but provide exciting potential treatment options; others have proved disappointing in larger extended-phase studies.

Keywords::

• disease-modifying therapy
• immunomodulation
• immunosuppression
• MS
• multiple sclerosis
• neuroprotection
• stem cell transplantation
• T-cell vaccination