A Prospective Study of Individuals at Risk of Multiple Sclerosis Informs the Design of Primary Prevention Studies

Area of Science:

• Neurology
• Immunology
• Genetics

Background:

• Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
• Early intervention is key to preventing irreversible neurological damage.
• Identifying individuals at high risk for MS is essential for developing primary prevention strategies.

Purpose of the Study:

• To examine the conversion rate of asymptomatic first-degree relatives of MS patients to an MS diagnosis.
• To evaluate an updated Genetic and Environmental Risk Score (GERS) for predicting MS risk.
• To assess the willingness of at-risk individuals to participate in primary prevention trials.

Main Methods:

• Prospective nationwide study (Genes and Environment in Multiple Sclerosis - GEMS project) of first-degree relatives of MS patients.
• Analysis of data from seven surveys over 11 years, including 1903 participants who completed all questionnaires.
• Collection of biological samples from a subset of participants for genetic analysis.

Main Results:

• The incidence rate of MS among first-degree relatives was 211 per 100,000 person-years, approximately 100 times higher than sporadic MS.
• A higher GERS was significantly associated with an MS diagnosis at enrollment.
• 48% of asymptomatic participants were willing to join a prevention trial, increasing to 75% when presented with elevated genetic risk information.

Conclusions:

• Primary prevention trials for MS are urgently needed.
• The high incidence rate in first-degree relatives supports the feasibility of such trials.
• Findings inform the design of future primary prevention trials for individuals at high risk of MS.