Recommendations for Multiple Sclerosis Prevention Published

Multiple sclerosis (MS) impacts over three million individuals globally. Recent advancements in treatments and a clearer understanding of key risk factors have provided new avenues for MS prevention. Historically, only six percent of global MS research funding has been dedicated to prevention efforts. However, discoveries in MS research and successes in delaying or preventing other immune-mediated diseases indicate that MS prevention is an achievable objective.

Global Prevention Workshop

In April 2025, a Global Prevention Workshop, co-sponsored by MS Canada and MS Australia, gathered approximately 60 experts in Lisbon, Portugal. The workshop focused on current knowledge and priorities for MS prevention. Recommendations derived from this workshop were subsequently published in the MS Journal.

Dr. Pamela Valentine, President and CEO of MS Canada, stated that the initiative aims to enhance understanding of MS risk, facilitate earlier diagnosis, and enable timely intervention.

Framework for MS Prevention

To establish targets for MS prevention, experts mapped the disease's evolution. Biological processes leading to MS can commence years before the onset of clinical symptoms. This progression involves genetic risk factors, environmental triggers that interact with these genes, and the eventual manifestation of MS symptoms. A deeper understanding of these processes could facilitate earlier detection and the development of strategies to prevent, slow, or halt MS progression.

Categorization of Prevention Strategies

Potential interventions to prevent MS are grouped by timing:

• Primordial prevention: Aims to prevent the development of MS risk factors, such as obesity or infectious mononucleosis, before they occur.
• Primary prevention: Involves targeting existing risk factors, such as low vitamin D levels, to prevent the onset of the disease.
• Secondary prevention: Focuses on detecting MS in its earliest stages to delay or prevent progression, thereby halting the disease from advancing.

Primordial and Primary Prevention: Addressing Risk Factors

The workshop addressed several questions concerning primordial and primary prevention, including prioritization of individuals and risk factors, the significance of timing, and intervention effectiveness.

• Genetic Risk: Over 230 genes are linked to MS risk, many of which are also present in individuals without MS. While genetic factors cannot be altered, they may assist in identifying individuals at higher risk for focused monitoring and in understanding the initial stages of MS. Current evidence predominantly originates from white European populations, indicating a need for broader research.
• Environmental Risk Factors: These include Epstein-Barr virus (EBV) infection, childhood and adolescent obesity, insufficient sunlight exposure, low vitamin D levels, and cigarette smoking. Recent research suggests that EBV infection is a necessary precursor for MS development, making it a potential target for prevention through vaccines or antiviral medications.

A multi-pronged approach that targets multiple modifiable risk factors was recommended. Emphasis was placed on acting upon current knowledge, focusing on modifiable factors, establishing coalitions, and presenting the economic justification for prevention.

Secondary Prevention: Early Detection

Similar questions were posed for secondary MS prevention: when, how, and in whom to intervene to delay or prevent MS.

Years before clinical symptom onset, a 'biological onset' of disease processes occurs. Some individuals experience a 'prodromal' phase, characterized by non-specific symptoms like headache and increased healthcare usage.

Currently, detecting the pre-symptomatic or prodromal stage of MS in real-time is challenging. However, promising blood markers, such as indicators of nerve damage and antibodies against brain proteins or EBV, may facilitate very early detection of MS, offering a window for intervention.

Continued work is recommended to identify and validate early detection markers, particularly for changes in the immune system. Further research is necessary to correlate these markers with long-term outcomes, which will require collaborative, long-term studies and the establishment of high-risk cohorts for future intervention studies. Global accessibility and affordability of early detection tools are considered critical for designing feasible clinical trials to delay or prevent MS.

Intervention Strategies for MS Prevention

The workshop explored the potential effectiveness of various intervention types:

• Population-level interventions: These offer broader reach but lower intensity, such as public health initiatives to reduce smoking or obesity.
• Individual-level interventions: More intensive and targeted, these can include short-term protective treatments (e.g., EBV vaccines), longer-term therapies (e.g., vitamin D, immune therapies), or support for lifestyle modifications.

Successes in other autoimmune diseases, such as type 1 diabetes, where early detection via blood markers has led to trials of early immune therapies successfully delaying disease onset, serve as a model. Effective MS prevention is expected to require multi-level interventions adapted to local contexts and life stages.

Ethical considerations were identified, including informing individuals found to be at higher risk of MS without immediate treatment options, evaluating potential risks of early treatments, and understanding the perspectives of people living with MS regarding preventive interventions for their children, if available. Ethical principles are to be developed to guide researchers identifying high-risk individuals or those with very early MS. Implementing MS prevention globally also necessitates building capacity in low-resource regions and prioritizing affordable, scalable interventions.

Requirements for Prevention Implementation

Measurement of Success

Evaluating the success of future prevention strategies is essential. This includes assessing engagement and uptake of interventions, as well as impacts beyond reducing new MS cases, such as reduced school/work absences and economic evaluations like lower healthcare costs.

Coalitions Across Sectors and Stakeholders

Building cross-sector coalitions is critical for MS prevention, enabling resource pooling, awareness building, communication facilitation, and policy advocacy. Diverse stakeholders, including individuals with MS, those at risk, MS organizations, groups addressing similar risk factors for other conditions, and public health agencies, are considered essential for developing effective interventions.

Communication Plan

A comprehensive communication plan is vital for disseminating information on existing risk factors and strategies for early detection and intervention among all stakeholder groups.

Future Directions

Preventing MS will necessitate long-term, well-coordinated global efforts, building on current understanding of MS disease processes. Prioritizing and funding key areas, forming international coalitions, and collaborating with global initiatives, such as the Pathways to Cures Initiative, are considered essential for achieving this objective.