Progressive MS Research

In progressive stages of MS, there are few or no relapses, and few or no recovery or remission periods when major symptoms improve.  Some of the burning questions that are being addressed through research include:
• What factors influence the transition from relapsing stages of MS to progressive MS?
• Can the disease-modifying therapies prevent, delay, or slow long-term MS progression?
• What new therapies will stop progressive MS?
• What causes degeneration of nerve fibers—thought to be the cause of long-term disability—and how can that be stopped or reversed?

But the landscape is changing, thanks in part to National MS Society investments and collaborations:

• The FDA approved Ocrevus™ (ocrelizumab - Genentech, a member of the Roche Group) for the treatment of primary progressive MS or relapsing MS, based on clinical trials showing significant benefits against MS relapses and progression. The Society funded early research that laid the groundwork for this first therapy specifically approved for primary progressive MS.
• A phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Secondary endpoints suggested that those on active therapy had less decrease of brain tissue volume.
• The therapy was generally well tolerated and similar to adverse events reported for similar compounds.

• The Society is funding several clinical trials of nervous system-protecting approaches:
  • Determining whether a biomarker can monitor the benefits of oxcarbazepine (epilepsy therapy) in people with secondary-progressive MS
  • The MS-SMART trial is testing three therapies that may have nerve-protecting properties in secondary-progressive MS (with the MS Society of the U.K.)
  • A unique collaboration between NIH's NeuroNEXT Network and MediciNova for a trial (SPRINT-MS) of ibudilast, an oral anti-inflammatory agent, in 250 people with progressive forms of MS.
  • A multicenter trial in the UK is testing whether a repurposed cholesterol-lowering therapy can slow the course of secondary progressive MS, with funding from the Society, the National Institutes for Health Research (UK) and the UK MS Society.  

• Large clinical trials are ongoing in progressive MS, including tests of masitinib and laquinimod.
• The International Progressive MS Alliance, an ever-expanding alliance of organizations from around the world, launched a €23 million global effort to end progressive MS, funding investigators from Canada, France, Germany, Israel, Italy, The Netherlands, Switzerland, UK and US. progressivemsalliance.org
• More than 30 studies investigating benefits of exercise, rehabilitation and other non-pharmaceutical strategies to enhance wellness, and address other symptoms that can interfere with quality of life. The Society has launched a wellness initiative to develop strategies for increasing high-quality research and programming so people with MS can make informed lifestyle and wellness choices that help them live their best lives.

•  The Society-supported MS Outcome Assessments Consortium is working on a new measure of MS disability to improve the chances of successful clinical trials in MS, including progressive MS.

Researchers are exploring mechanisms that drive injury to the brain and spinal cord to expose new potential therapeutic targets along the injury pathways that may stop the damage. These include:

• Large-scale studies tracking people with MS to identify factors that contribute to progression risk.
• Advanced imaging and laboratory studies seeking to define and track the full measure of MS disease activity, MS lesions, and atrophy (shrinkage) in the brain and spinal cord.
• Exploring the potential of different types of stem cells to repair the nervous system in models of the disease, and ways to enhance the survival of repair cells in inflamed and scarred nerve tissue.

• Researchers from the U.S. and Spain funded by the Society found that comparing the levels of two molecules in the brain detected with a form of MRI scanning was able to reliably predict MS progression in two independent groups of people with MS. This may be a useful tool for tracking the benefits of potential treatments in clinical trials aimed at protecting the nervous system from damage.
• A team from the University of Connecticut co-funded by the Society report that nerve stem cells programmed from the blood of people with primary progressive MS did not protect mice from injury of nerve-insulating myelin and did not promote myelin repair, compared to cells from people without MS.
• Experts were convened by the National Institute of Neurological Disorders and Stroke and the National MS Society to evaluate how MS “cohorts” – studies designed to track people with MS over time – might be leveraged to answer urgent questions about what causes progressive MS and how to stop it.
• An international team led by Harvard researchers co-funded by the Society has found that levels of vitamin D in serum early on in MS may predict later disease activity and progression.
• Researchers at Brigham and Women’s Hospital funded by the Society found in a large-scale, long-term study of women that progression changed at or around menopause toward a more rapid accumulation of disability, offering clues to further research and intervention
• A trial at University College London, funded by the MS Societies of the US and UK showed that people with inflammation of the optic nerve who were taking the epilepsy treatment phenytoin had 30% less optic nerve damage compared to placebo. The results need confirmation in a larger study.
• Collaborating researchers from the U.S. and Germany funded in part by the Society through Fast Forward reported promising early lab results from a new class of compounds that have potential for both protecting the nervous system and turning off immune attacks, possibly slowing MS progression.

We are relentlessly pursuing the answer to this question each and every day. Identifying and moving solutions forward is how we will succeed in stopping the progression of MS.

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