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?

A common question is, “Why aren’t there more treatments for progressive MS?”  Virtually every therapy approved for relapsing MS has been tested, or is now in testing, in people with progressive forms of the disease. Clinical trials involving people with relapsing MS often rely on counting relapses or doing MRI scans to detect immune activity. Progression is less easily measured, and usually happens over long periods of time. This important difference makes it hard to quickly detect whether a therapy is impacting progression, and thus has made therapy development for progressive MS a challenge.
 
But the landscape is changing, thanks in part to National MS Society investments and collaborations:

• The Progressive MS Alliance is bringing together the world’s leading experts in multiple sclerosis to change the world for people with progressive MS.
• 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.
• The FDA approved oral siponimod (brand named Mayzent,^® Novartis International AG) for the treatment of adults with clinically isolated syndrome (an initial neurological episode) and relapsing forms of MS, including those with active secondary progressive MS. This means people who have had progression of disability but still experience acute relapses or new MRI activity.
• The Society has provided funding to several clinical trials of nervous system-protecting approaches:
  • The ChariotMS trial in the United Kingdom, which will test whether cladribine tablets (Mavenclad®) can slow the progression of upper limb disability in people with advanced MS, who are rarely included in clinical trials
  • Results have been published of a phase 2 trial of oral ibudilast (MN-166, MediciNova, Inc.), in people with progressive forms of MS suggested it significantly slowed the rate of brain atrophy (shrinkage), which has been linked to cognitive and physical disability in MS. Ibudilast has been designated by the FDA as a “Fast Track Product” in terms of its development as a possible treatment of progressive 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 oral "BTK inhibitors," which affect activation of immune cells.
• 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 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.

• An international research team supported by the Alliance and the Society found no difference in the behavior of OPCs derived from MS skin cells and those from healthy individuals, implying that MS does not change the inherent capacity of oligodendrocytes to repair myelin, and that the fault is more likely the brain environment. 
• Researchers at Johns Hopkins University studied small molecules involved in the metabolism (chemical processes that maintain cell life) of people with MS and people without MS, and found that molecules called bile acids were reduced in people with MS, particularly those with progressive disease. Bile acids have anti-inflammatory and neuroprotective properties. This team is planning a trial of bile acid supplementation in 60 people with progressive MS, with funding from the National MS Society.
• 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.
• The MS-SMART trial tested three therapies that may have nerve-protecting properties in secondary-progressive MS (with the MS Society of the U.K.) Although none of the therapies slowed brain atrophy, the results confirm the feasibility of this innovative multi-arm trial design, enabling much quicker assessments of potential therapies for progressive MS in the future.

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.