National MS Society Details Steps to Achieving Pathways to Cures

The National Multiple Sclerosis Society (NMSS) has detailed its Pathways to Cures Roadmap and potential ways of addressing gaps and advancing each of the pathways, with a final goal of finding a cure for multiple sclerosis (MS) in all its forms.

Details were in the report, “Pathways to cures for multiple sclerosis: A research roadmap,” published in the Multiple Sclerosis Journal.

“Curing MS is within our reach,” and “when we talk about curing MS, we’re talking about curing MS for everyone,” Bruce Bebo, PhD, executive vice president of research at the NMSS and the report’s first author, said in a press release.

“The roadmap, now endorsed by over 20 national and international MS organizations, will drive progress by increasing alignment and focus of global resources on high priority research questions,” Bebo added.

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“While substantial progress has been made in the development of more than a dozen effective disease-modifying treatments (DMTs) for relapsing forms of MS, we still lack a fundamental understanding of all the … processes driving disease, we lack effective treatments for progressive forms of MS, and cures remain elusive,” its authors wrote.

With this in mind, the NMSS developed the Pathways to Cures Roadmap to highlight the knowledge gaps, key objectives, and research priorities that will advance each pathway and speed the development of potential cures.

The roadmap was created through a consensus-building process involving the society’s advisory committee, national board of directors, and Pathways to Cures task force — which included scientific experts, healthcare providers, and people affected by MS from the U.S., Canada, and the U.K.

The perspectives of more than 300 MS patients, collected through a survey, were also incorporated into the roadmap, which was subsequently endorsed by MS patients and professional organizations worldwide.

Supported by $13 million in funding from investors, the roadmap includes three distinct but overlapping pathways: STOP, stopping MS in its tracks; RESTORE, restoring what has been lost; and END, ending MS by preventing new cases.

STOP pathway

This pathway’s goal is to halt disease activity and progression — and therefore worsening of daily life or quality of life — for those who already have MS. It aims to strengthen chances for restoring neuronal health and patients’ overall function.

To achieve this goal, research should focus on improving early detection — as early treatment is associated with better outcomes — and precision medicine given the high level of disease variability between patients.

Since increasing evidence supports the existence of an MS prodrome, a set of signs or symptoms that occur before the onset of typical symptoms of a disease, future studies are needed to determine its underlying mechanisms. Such efforts would help identify biomarkers of early disease to improve diagnoses and support early treatment.

Better biomarkers, as well as predictive models, are also needed to better understand the mechanisms behind distinct MS disease courses and to help select the best therapy “for a given patient at a given point in time,” the researchers wrote.

Effective therapies for progressive forms of MS are another large unmet need, and research should also focus on these.

RESTORE pathway

This pathway aims to repair and reverse nerve damage and restore function that patients have lost — effects that current DMTs generally lack.

Research should focus on identifying molecular targets that promote nerve cell and myelin repair (remyelination), as well as outcome measures of remyelination and/or functional recovery to be used in clinical trials. Myelin is the protective fatty sheath around nerve fibers that is progressively lost in MS.

Another high unmet need is for clinical trials testing functional recovery, symptom management, rehabilitation, and wellness interventions. Exercise is increasingly seen as a promising approach to ease motor and non-motor symptoms of MS, and wearable devices may help to monitor function and intervention benefits.

“An integrated approach is needed that enhances remyelination, neural regeneration, and neuroplasticity [re-wiring of brain connections], while optimizing the extent to which wellness behaviors, rehabilitation, self-care, and exercise promote reversal or diminution of symptoms,” the researchers wrote.

END pathway

The two main objectives of the END pathway are preventing MS in the general population (primary prevention) and identifying MS in its prodromal stages to delay or prevent disease onset (secondary prevention).

More studies are needed to identify all the modifiable risk factors of MS in all populations, including environmental exposures and social determinants of health, meaning the conditions under which people are born, grow, live, work, and age.

“A better understanding of all [risk] factors and their interactions that can trigger MS, as well as cooperation and buy-in by public health agencies and policy makers to the concept of MS as a preventable disease are needed,” the researchers wrote.

The goal is to limit exposure to such risk factors, such as low vitamin D levels, adolescent obesity, tobacco smoking, and Epstein-Barr virus infection.

Early biomarkers and screening tools are also needed to identify people at higher risk (prodromal phase) so that appropriate interventions can be taken before symptom onset to lessen or eliminate the impact of MS.

Among general recommendations, the authors highlighted the need to increase participation of racial and ethnic minorities as underrepresented groups in MS research.

“Improved engagement of these groups will lead to improvements in the quality of scientific data, facilitate the discovery of important efficacy and safety information and help to identify population specific differences in disease course and treatments and accelerate the development of cures for everyone with MS,” they wrote.

“We hope the Roadmap will inspire greater collaboration and alignment of global resources that accelerate scientific breakthroughs leading to cures for MS,” the researchers added.

The NMSS stated that this roadmap will be updated every two years to reflect advances in these pathways and to account for the development of new technologies and approaches.

“We look forward to partnering with other global stakeholders in the MS movement to make the hopes and dreams of people with MS around the world come true,” the researchers wrote.

The NMSS is in the process of supporting research projects aligned with the Pathways to Cure Roadmap.