2023-06-28 カロリンスカ研究所(KI)
◆MSは20歳から40歳の間に発症し、免疫系が脳と脊髄を攻撃することによって起こります。既存の治療法は発作を抑えることができますが、障害の進行を確実に防ぐことはできません。
◆この研究は、米国UCSF、英国ケンブリッジ大学、スウェーデンのカロリンスカ研究所の研究者によって行われ、病気の重症度を増大させる遺伝的変異が特定されました。この変異を両親から受け継ぐと、歩行補助具が必要になるまでの時間が4年近く短縮されます。この発見は、MS患者にとって急務の進行抑制の新しい治療法の開発の可能性を示しています。
<関連情報>
- https://news.ki.se/new-gene-discovery-gives-hope-of-fighting-severe-ms
- https://www.nature.com/articles/s41586-023-06250-x
重症度の遺伝子座が多発性硬化症の進行に中枢神経系の回復力を関与させる Locus for severity implicates CNS resilience in progression of multiple sclerosis
International Multiple Sclerosis Genetics Consortium & MultipleMS Consortium
Nature Published:28 June 2023
DOI:https://doi.org/10.1038/s41586-023-06250-x
Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults1,2. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF–ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3–PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility3, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.
