Multiple sclerosis (MS) is a disease that affects the central nervous system, meaning the brain and spinal cord. MS is caused by the patient’s immune system attacking the tissue of the central nervous system, progressively leading to nerve damage. Consequently, communication between the brain and the rest of the body becomes disturbed, which causes a variety of neurological symptoms.
There is currently no cure for MS, yet some symptoms can be managed with treatment. The severity of MS symptoms and how quickly the disease progresses vary from patient to patient, making it a highly unpredictable disease. Over time, some patients may only experience mild symptoms, while others may lose the ability to walk, see, talk and write.
The answer to disease variation may lie in the genes
Knowing what causes such variation in disease progression can be valuable information for treating MS.
To address whether the cause could lie in the patients’ own genes, two large MS consortia came together to analyze genetic data from more than 22,000 MS patients from around the world. NCMM Director Janna Saarela and her research team in FIMM, Helsinki, contributed to the study by setting up and maintaining the largest harmonized, multi-modal data resources for Multiple Sclerosis to date.
Using advanced statistical analysis, the authors of the study were able to identify the first genetic variant that associated with a faster disease progression. The results were recently published in Nature.
Genetic variant can point to new drug targets
Patients with this specific genetic variant become dependent on walking aid nearly 4 years earlier than patients who do not carry this variant. The same patients also have more tissue damage in their central nervous system.
The identified genetic variant is localized between two genes called DYSF and ZNF638. These genes are involved in the repair of damaged cells and controlling viral infection, respectively. Since MS is characterized by tissue damage in the central nervous system and inflammation, it is possible that the genetic variant can influence MS progression by affecting these genes.
It is not yet known if these two genes are directly involved in MS disease progression. However, the identified genetic variant provides a new avenue for future studies aiming to understand the mechanisms of MS development, and possibly new drug targets.
Publication
International Multiple Sclerosis Genetics Consortium., MultipleMS Consortium. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature (2023). https://doi.org/10.1038/s41586-023-06250-x