POST-MORTEM MULTIPLE SCLEROSIS LESION PATHOLOGY IS INFLUENCED BY
SINGLE NUCLEOTIDE POLYMORPHISMS
Nina L. Fransen, Jakob B.A. Crusius, Joost Smolders, Mark R. Mizee, Corbert G. van
Eden, Sabina Luchetti, Ester B.M. Remmerswaal, Jörg Hamann, Matthew R.J. Mason, Inge Huiting
Brain Pathol. 2019 Jun 22. doi: 10.1111/bpa.12760
TAKE HOME POINT:Knowing which genes are associated with either a more course of MS or with a greater ability to heal or remyelinate may allow healthcare providers to personalize information regarding an individual’s prognosis and allow more informed treatment decisions regarding the best disease modifying therapy for that individual.
Key Points:
1. Genes play a critical role, in determining susceptibility to MS. They also are involved in determining severity of disease and an individual’s ability to heal MS lesions, i.e. remyelinate them.
2. Over 200 genes have been identified as being associated with MS. However, the role they play in the disease is not known.
3. The above paper describes the efforts of scientists to identify genes in MS that may be involved in affecting tissue damage in the central nervous systems of persons with MS.
4. The scientists studied 102 different genes in autopsy brain tissues from 179 persons with MS. The genes were chosen based upon their association with the clinical course of MS. Genes were identified based on variations in their DNA sequences called SNPs (“single nucleotide polymorphisms”).
5. The authors wished to see if any of these genes were associated with specific changes in MS brains.
6. The authors identified three genes that were associated with more active disease and three other genes that were associated with lesions in certain areas of the brain such as the gray matter, but also were associated with varying degrees of remyelination or lesion healing.
7. By showing that particular genes result in different patterns of tissue damage and tissue healing, it may now be possible to identify these genes in living individuals with MS, and thus possibly identify those persons at greater risk for more extensive tissue injury, but also those persons with MS that may have milder disease based in their ability to heal or remyelinate brain lesions.
8. Disease-modifying therapies for MS vary greatly, both in their intensity of immune suppression and in their toxicity, which can be severe. Being able to identify those persons at higher risk for more severe disease will allow choosing a disease-modifying therapy, with greater potential toxicity but also greater ability to control their illness.
There are great variations in the course of MS, ranging from severe disability within several years to minimal disability after decades. Reasons for such differences are not understood, but the above paper is an important addition to our understanding of why persons with MS have such great variability. We know that genes play an important role in determining not only susceptibility or risk for developing MS, but also for determining the course of disease. While correlations between particular genes and clinical course have been made in living individuals, this paper was able to identify genes that were associated with more tissue damage at autopsy, as well as other genes that were associated with different patterns of brain lesions, and finally 1-2 genes there were associated with healing of lesions, or remyelination. These observations fit in nicely with previous observations that some persons with MS have a greater ability to heal or remyelinate their lesions than others, resulting in a milder clinical course.
Cancer treatments were revolutionized when doctors learned that the genes cancers expressed determined their responses to chemotherapy. By identifying a particular cancer’s genes in an individual doctors are no able to prescribe a “personalized” treatment for that individual, an approach that has greatly extended the life-spans of many individuals. In the case of MS this is just “pie in the sky” conjecture at this time. However, personalizing treatment for persons with MS, by knowing which genes are associated with more severe disease and which genes are associated with less ability to heal, could allow healthcare providers to choose a particular disease modifying therapy best suited for that individual, in terms of potential benefits versus potential toxicities from the treatment.
The abstract of the article is available.