Researchers Gather for First Scientific Meeting of the International Progressive MS Collaborative – - National Multiple Sclerosis Society

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Researchers Gather for First Scientific Meeting of the International Progressive MS Collaborative – challenges and opportunities identified

February 27, 2013

More than 170 MS researchers recently met to discuss key challenges and strategies for accelerating the development of effective treatments for progressive forms of MS. This landmark meeting was convened by the International Progressive MS Collaborative, a joint effort of the MS International Federation and MS Societies of Canada, Italy, Netherlands, United Kingdom, and the United States. Download a summary with photos (.pdf)

Over the two-day meeting, participants debated the challenges that need to be overcome to identify therapies that can halt or even reverse MS progression. There was also discussion of many ongoing research efforts in progressive MS, suggesting that many of these challenges are already being tackled and that more attention will speed these efforts.

MS International Federation Board member and European MS Platform President John Golding (Fredrikstad, Norway) issued a “Call for Action” to meeting participants, recounting the uncertainties faced by him and so many others living with progressed MS. “Let these days be a new beginning for us all,” he said of the scientific meeting. 

Meeting co-chair Dr. Alan Thompson (University College London) noted that an estimated $85 million is being invested right now by MS societies around the world, in addition to what pharmaceutical companies are investing in several major clinical trials involving people with progressive MS. Co-chair Dr. Giancarlo Comi (Scientific Institute San Raffaele, Milan) also highlighted several initiatives already underway, such as MAGNIMS (MRI collaboration), the International Advisory Committee on Clinical Trials in MS, and the MS Outcome Assessments Consortium, which will help create tools to drive breakthroughs in progressive MS.

Five Priority Areas Discussed

The Collaborative had previously released a report that identified five key research priorities. Teams of scientific experts were convened to explore these priority areas, and at the Milan meeting they reported their findings and sought feedback from participants. Some highlights and takeaways include:

Identifying Targets and Repurposing Opportunities for Progressive MS
  • To date, large-scale genetic studies have identified more than 50 genes that influence susceptibility to MS, but so far, they have not uncovered genetic differences between relapsing and progressive MS, nor have any genes been identified that drive disease severity. Additional studies may determine the degree to which genes and the environment influence disease course and the body’s repair mechanisms.
  • Since a different part of the immune system is more prominent in progressive compared to relapsing MS, such as activity of brain cells called microglia, discovering ways to safely target this activity may be a productive approach to new therapies.
  • Developing treatments for progressive MS may be accelerated by testing therapies approved for other diseases involving nerve degeneration (repurposing). However, there need to be incentives and a clear pathway to enable off-patent drugs to be repurposed for progressive MS.
Experimental Models for Preclinical Evaluation of Therapies
  • Animal models of relapsing MS have been valuable for early testing of potential therapies. A deficiency of models of progressive disease has hindered development of therapies for progressive MS. Therefore there is urgent need for models that reproduce the clinical symptoms and underlying tissue damage seen in progressive MS.
  • Some existing models permit the study of specific aspects of progression, such as myelin damage and repair.
  • Progressive MS shows unique pathology such as spinal cord involvement, and oxidative injury, which accumulates with advancing age. More information about the pathology of progression and complications of aging can drive the development of new models for drug testing.
Proof-of-Concept/Clinical Trial Strategies
  • Testing new therapies in relapsing MS is facilitated by getting MRI signs of positive response in very short (six month) phase II trials. There is currently no equivalent 6-month readout to monitor success in progressive MS.
  • There is a need for “biomarkers” that measure nerve fiber injury or integrity and other factors contributing to progression of disability. There is growing evidence for using one candidate marker of nerve damage in spinal fluid, called neurofilament, as an early readout of neuroprotection. There is a European consortium (Bio MS) for research in spinal fluid biomarkers in MS, and participants noted the continuing need for trials to include spinal fluid testing to make them more informative.
  • There are emerging imaging biomarkers that can detect brain and spinal cord integrity that may be useful for both phase II and phase III trials in progressive MS.
  • New clinical trial designs are needed that minimize the number of participants and duration of trials so that more therapies can be tested more quickly at lower cost. There was exciting discussion of a new trial in secondary-progressive MS getting underway in the U.K. that is using a novel “adaptive” design.
Clinical Outcome Measures and Trial Design
  • There is a need for better ways to measure improvement and success of therapies in progressive MS. The ideal measurement would be sensitive to change over time, and predictive of future change. There is an international effort already underway to create an improved outcome measure for MS clinical trials – read more
  • New technologies are being explored, such as smartphones and tablets, for their potential to measure real-time impacts of treatments on daily activities and mobility.
  • Participants noted the need to better classify different types of progressive MS, to improve the chances of favorable outcomes from clinical trials.
  • It will be important to account for co-morbid diseases (such as heart disease, obesity, etc.) and environmental/lifestyle factors of trial participants that could influence individual responses to treatment and trial outcomes.
  • More information could be gleaned by exploring data from previous clinical trials, patient registries and databases to help inform new trial designs and biomarkers.
Symptom Management and Rehabilitation
  • Exercise looks like a promising approach with potential for both physical and cognitive benefits. Research is needed to determine ways to keep people exercising beyond time-limited supervised programs.
  • More well-controlled, larger trials are needed to evaluate symptomatic therapies and rehabilitation methods, particularly cognitive rehabilitation interventions.
  • When testing therapies to treat cognitive impairment, a person’s lifetime intellectual enrichment may influence outcomes, since those with higher “cognitive reserve” may fare better.
  • There is an urgent need for symptom management and exercise programs to improve quality of life for those who are severely impacted by MS progression.
In concluding remarks, MSIF Chair and National MS Society National Advisory Council member Weyman Johnson (Athens, Georgia, USA) shared his experience as a person with MS and who has multiple family members who’ve had MS. “There are obvious scientific challenges, and challenges in international efforts. But it is extremely important that this move forward as a global effort.”

As meeting co-chair Dr. Alan Thompson noted, “We are addressing one of the most challenging aspects of research in MS: understanding and treating progressive MS.”

IPMSC leadership is evaluating the advice given by participants and are developing an action agenda that will be shared later this year.

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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