Can MS Be Prevented? Perhaps, But......
- Gary Birnbaum, MD
- 3 days ago
- 4 min read
Towards primary prevention of multiple sclerosis
Dobson, R., Kreft, K.L., Jacobs, B.M., Brown, J.W.L., Thomson, A., Nicholas, R., Walton, C., Narendran, P. & Taskforce, U.M.P.
Nat Rev Neurol; Volume 22; March 2026; Pgs.182-195
Introduction:
Treatment of multiple sclerosis has changed dramatically in the past several decades with the development of disease-modifying therapies that greatly ameliorate but not cure the illness. The cause of the disease remains unknown, nor do we know exactly when the illness begins. The closest we have to making the diagnosis early and initiating therapy are in persons with radiologically isolated syndrome, a condition when changes of MS are noted on central nervous system MRIs, but no symptoms related to the changes have occurred.
The ideal approach would be prevention of multiple sclerosis by treating modifiable factors that not only increase risk but are intrinsic to the initiation of the illness. This approach has been dramatically successful in preventing cardiac and vascular disease. The above paper proposes that there are sufficient data to now begin to design and implement clinical trials testing interventions that may prevent the development of the inflammation that results in central nervous system tissue destruction. The parameters for such trials and initial interventions that could be studied are excellently detailed in the paper and more briefly discussed below.
Key Points:
1. Any trial studying the prevention of multiple sclerosis will need to last years to decades. Thus, participants must commit to long-term testing and follow-up.
2. Since we don’t know when the initiating events of MS begin, study participants may need to enter a study as children, and possibly even as newborns.
3. MS is a relatively uncommon disease that varies with geographic location, sex, and family history. To minimize the numbers of persons needed for study the trial cohort must have the highest risk of developing MS. Thus, it must be persons living in higher-risk latitudes with strong family histories of MS. However, since most cases of MS are sporadic, with no family history, this cohort of persons, with sporadic MS, cannot be studied.
4. Recruitment of trial participants that meet eligibility criteria for latitude and family history, and that are willing to participate in such a long-term study, will be difficult. It will require a multinational, and even a world-wide effort. Given the great disparities in healthcare and systems of health management, it will be essential that all study sites commit to identical measures of testing physical, blood, diet and MRI parameters.
5. Funding for such a long-term study will be a challenge, but it can and has been done. An example is a study of Type 1 diabetes mellitus, where unique antibody profiles were found in healthy relatives of persons with Type 1 diabetes that predicted the development of the illness. Antibody signatures predictive of developing clinical arthritis also are described, and preliminary results have described unique antibody responses to panels of proteins that appear predictive for the subsequent development of MS.
6. Retrospective studies have suggested that prodromal symptoms precede the development of MS. While these are important observations, the prodromal symptoms noted are relatively non-specific, and could result from disease processes other than MS. Thus, at this time using described prodromal symptoms to identify persons at risk for developing MS is not possible.
7. While there are well-described genetic susceptibilities, most individuals with these susceptibility genes do not go on to develop MS, so using genetic screening alone to identify persons with a high risk of developing MS alone is not feasible. Nevertheless, genotyping of persons with the other risk factors described above needs to be done, since responses to modifiable risk factors could vary with genotype.
8. Critical to the success of any study designed to prevent MS is to identify modifiable risk factors that may contribute to disease pathogenesis. While we don’t know with certainty the inciting events of the illness, some risk factors are well described. These include childhood obesity, low vitamin D levels, low exposure to sunlight, infection with Epstein-Barr virus, development of infectious mononucleosis and smoking, both in parents and offspring.
9. The challenges of initiating a clinical trial to prevent MS, addressing the modifiable risk factors noted above, are substantial. Multinational cooperation, use of remote accessing of data (electronic health records), remote collection and storage of biologic samples (blood, urine, tears), periodic, standardized MRI imaging methodology, and pre-defined primary and secondary endpoints will be essential for the preventive trial’s success.
Discussion:
The authors of the above paper propose there are sufficient modifiable risk factors implicated in the development of MS that a clinical trial aimed at identifying persons at high risk for MS and instituting measure to control risks is feasible.
Some modifiable risks are easily addressed. Reducing smoking exposure, both in utero and beyond, is feasible. Use of glucagon-like peptide 1 agonists (GLP-1 drugs) can effectively relieve obesity. Vitamin D supplementation early in life could be initiated. More controversial is the administration of vaccines to prevent Epstein-Barr virus infection.
Epstein-Barr virus infects over 90% of the population, and most infections are asymptomatic. The virus and its analogues have been around for millions of years, and have infected multiple species other than humans. This raises the possibility that infection with Epstein-Barr virus may have protective benefits, benefits that preventative vaccination could thwart, with unexpected consequences. Several recent publications have discussed these issues. The other unknown, if anti-Epstein-Barr virus vaccination is chosen for study, is when to vaccinate. Should it be at birth, or should one wait for additional maturation of the person’s immune system?
The ability to prevent MS, initially, in high-risk populations, but hopefully later in the general population, would be a major accomplishment, not only in terms of this disease, but as a paradigm for addressing modifiable risks in other neurologic illnesses. Achieving this goal will take years, and possibly decades. New MS-related risk factors may may be discovered over the years and modifying them could be added to ongoing prevention trials. The challenges are great, but the end result could reduce, and possibly eliminate the most common, and potentially ravaging, inflammatory central nervous system disease of young adults.
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