While much progress has been made in the understanding and treatment of multiple sclerosis (MS) over the last several decades, we continue to focus on investing in research that can lead to cures for MS. Through a consensus building process, the National MS Society in the USA sought input from scientific experts, health care providers, and people affected by MS from the United States, Canada and the United Kingdom to develop a research roadmap that identifies pathways to cures for MS. Many MS global organizations, including the MS Society of Canada, have endorsed this roadmap.
The roadmap consists of three cure pathways:
STOP: Stopping the MS disease process. This would result in no new disease activity or central nervous system injury, no worsening of daily living or quality of life, and no change in disease manifestations. This would prevent the accumulation of disability and create a permissive environment for myelin and axonal repair and other pathways that promote restoration of function.
Recommendations to address gaps:
- Understanding of the mechanisms driving the MS prodrome – the early non-specific signs or symptoms of the disease prior to MS onset – to improve diagnoses and support early treatment.
- Biomarkers and tools to better understand the biological differences in MS disease course in individuals.
- Tools that support the selection of more precise interventions and therapeutic approaches (e.g. precision medicine).
- Therapies for progressive forms/stages of MS.
RESTORE: Restoring lost function by reversing damage and symptoms. While disease-modifying therapies (DMTs) limit the occurrence of relapses and in some cases delay disability worsening, they have limited capacity to enhance or restore function. There is a need to enhance regeneration and remyelination as well as focus on strategies to manage symptoms and improve quality of life.
Recommendations to address gaps:
- Understand the physiological mechanisms involved in regeneration and repair (i.e. understand roles of aging, sex, genetics and other factors associated with regeneration and repair of damaged nerve fibres).
- Identify outcome measures that are sensitive to regeneration and/or functional recovery.
- Trial designs that foster the development of rehabilitation and wellness interventions.
- Use of standard outcomes across clinical trials.
END: Ending MS through prevention. This would mean no new cases of MS. This pathway aims to prevent MS in the general population, also known as primary prevention. This would reduce or eliminate exposure to environmental risk factors (e.g. low vitamin D levels, adolescent obesity, tobacco smoking, infection with Epstein-Barr virus) and more targeted measures for those at higher risk of developing MS. This would also include secondary prevention, identifying MS in the earliest stages (e.g. prodromal phase) to delay or prevent onset of the disease.
Recommendations to address gaps:
- Knowledge of MS risk factors that are necessary and sufficient to cause MS and the time frame for exposure.
- Public health interventions that reduce or eliminate exposures to MS risk factors.
- Complete understanding of the genetic and epigenetic (non-genetic influences on gene expression) contributions to MS risk and contribution to disease onset.
- Elucidate the pathological pathways contributing to the initiation of MS.
- Biomarkers (fluid/imaging/clinical indicators) that identify people at high risk for developing MS.
- Identification/implementation of interventions that prevent onset of MS in the high-risk population.
This roadmap aims to provide opportunities for greater collaboration and alignment of global resources to accelerate scientific breakthroughs leading to cures for MS. This roadmap will be updated biennially to reflect advances in these pathways and to account for the development of new technologies and approaches.
References:
Bebo BF, Allegretta M, Landsman D, et al. Pathways to cures for multiple sclerosis: A research roadmap. Multiple Sclerosis Journal. 2022;28(3):331-345. doi:10.1177/13524585221075990