Global research agenda to end progressive MS

  • Progressive MS affects over 1 million people worldwide, with only a few modestly effective treatments approved. The International Progressive MS Alliance has surveyed the current research landscape, including factors influencing MS progression and experimental treatments in development.
  • Their global research strategy identified three gaps that must be addressed to accelerate progress: understanding the underlying causes of MS progression, speeding up clinical trials and improving wellbeing.
  • A more coordinated approach is needed to allow people with progressive MS, research funders, academic researchers, the pharmaceutical industry, and drug regulators to work together to address these gaps.

Background to the strategy

Progressive MS includes both primary progressive MS and secondary progressive MS and affects over 1 million people worldwide. In contrast to relapsing remitting MS, where there are periods of worsening symptoms with an acute relapse and then a possible return to baseline function after recovery, progressive MS involves a gradual worsening of symptoms over time. There appear to be different biological mechanisms driving progressive MS: while relapsing remitting MS is primarily driven by active inflammation, progressive MS is thought to develop due to a combination of factors, including brain and spinal cord damage from inflammation, nerve degeneration, and ageing.

There have been great leaps in the treatment of relapsing remitting MS in recent years. In contrast, treatment for progressive MS has lagged, with a few approved treatments that are only modestly effective. The International Progressive MS Alliance (“The Alliance”) was formed to rally the global community around the unmet needs of the more than 1 million people with progressive MS worldwide. MS Australia is embedded in this collaboration as a founding and managing member. The Alliance has now developed a detailed set of priorities and plans to overcome gaps in the treatment and management of progressive MS. Charting a global research strategy for progressive MS—An International Progressive MS Alliance proposal was published in December 2021 as a free, open-access resource.

What has already been achieved in progressive MS research?

The Alliance’s Scientific Steering Committee conducted a major review of the scientific literature to summarise current knowledge and identify gaps. Since their first strategy paper in 2012, they noted there have been major changes, including the approval of the first treatments for progressive MS: Ocrevus (ocrelizumab) for primary progressive and Mayzent (siponimod) for secondary progressive. We now have a better understanding of the factors that influence progression, including gender, ethnicity, socioeconomic status, genetics, other co-occurring diseases, and the use of disease modifying therapies. Clinical trials of experimental therapies have suggested that progressive phases of MS are responsive to treatment. Within the paper is a graphic showing over 50 experimental treatments in clinical trials for various aspects of progressive MS (in April 2021). These include drugs or interventions targeting immune mechanisms, nerve protection, repair of the myelin sheath around nerves (that is damaged in MS), symptom management, rehabilitation and quality of life. Also included were trials for the discovery of reliable biological markers to better assess MS progression, such as new blood tests or brain imaging.

What are the critical next steps to solve progressive MS?

The team identified three major gap areas with potential to accelerate the path to better treatments:

  1. The first gap exists in understanding the biology driving disease progression. Gaining a deeper knowledge of the underlying causes will uncover new treatment targets to slow, prevent, and even reverse disability. The team recommended increased fundamental research in this area using animal and human studies; robust data sharing with machine learning and other artificial intelligence tools to gain new insights. They also recommended the use of biological markers to better describe the disease course – an effort that is already underway.
  2. The second major focus is to speed up clinical trials for progressive MS. MS progression is generally slow, and therefore there is no fast way to detect whether an experimental therapy is working. To increase our capacity for fast, efficient trials of potential new therapies, new clinical trial designs are needed. Changes may include trials requiring fewer participants, having multiple arms to test multiple therapies at once, having flexibility to change the trial if a therapy is clearly not working, as well as developing reliable tests to assess early whether a treatment is working. These might be fluid markers (e.g. blood tests), new brain imaging markers, or defined clinical outcomes. The MS-SMART trial of three agents in progressive MS and the recently launched OCTOPUS trial are encouraging examples of this new approach.
  3. The third area requiring more attention is testing and sharing effective ways to improve wellbeing for people with progressive MS. There is great scope to improve rehabilitation and symptom management to target physical, cognitive, and emotional health symptoms in progressive MS. Addressing co-occurring health problems and providing better social support is also key. The recently launched COGEx clinical trial is the first multi-country, multi-arm, controlled trial of cognitive rehabilitation and aerobic exercise, which is an excellent example of the kind of work needed to improve wellbeing in progressive MS.

The importance of joining forces

The authors highlighted the need for all parties, including people affected by progressive MS, research funders, academic researchers, the pharmaceutical industry, and drug regulators to be engaged, be aware of the challenges, and work toward a more coordinated approach to solving them.

Professor Alan Thompson is the Pro-Provost and Dean of the Faculty of Brain Sciences at University College London and the first author on the paper. He said, The publication of this paper is an important step toward a more coordinated, global approach to tackling challenges and realizing opportunities for improving quality of life for people living with progressive MS.”

Dr Julia Morahan is Head of Research at MS Australia, a member of the Alliance Scientific Steering Committee and co-author. She added, “The International Progressive MS Alliance has been very successful at bringing together global stakeholders and aims to tackle the problem head-on at multiple levels: the underlying biology of progression, clinical trials and wellbeing for those living with progressive MS. This is our best chance to fast-track solutions for all those with progressive disease.”


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Global research agenda to end progressive MS