{"id":647251,"date":"2026-10-15T15:00:09","date_gmt":"2026-10-15T15:00:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/il\/647251\/"},"modified":"2026-10-15T15:00:09","modified_gmt":"2026-10-15T15:00:09","slug":"loi-modifier-linked-to-neuron-loss-in-huntingtons-disease","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/il\/647251\/","title":{"rendered":"LOI Modifier Linked to Neuron Loss in Huntington\u2019s Disease"},"content":{"rendered":"

In a study published in\u00a0Neuron<\/a>, Chris Kay, PhD, of the University of British Columbia in Vancouver, and colleagues assessed somatic\u00a0HTT\u00a0CAG expansion in peripheral blood, postmortem brain tissue, and isolated MSNs from patients with HD, both with and without the CAG-CCG loss-of-interruption (LOI) modifier variant.<\/p>\n

Results showed that, while MSNs with large (111\u2013150 CAG) and very large (>150 CAG) somatic expansions were rare early in HD, these larger expansions accumulated as disease duration increased.<\/p>\n

The CAG-CCG LOI modifier was linked with about a five-fold increase in the proportion of MSNs with large and very large expansions. Patients with the modifier also had fewer caudate MSNs, suggesting the modifier accelerates MSN loss alongside increased somatic CAG expansion.<\/p>\n

The modifier was also linked with reduced small somatic expansions in the blood. As a result, the authors note that blood DNA is likely a poor biomarker for disease-relevant somatic expansion in HD.<\/p>\n

Overall, these findings suggest that genetic changes to the\u00a0HTT\u00a0CAG repeat can modify HD pathogenesis by altering the rate of large somatic CAG expansions. At the same time, results show that some MSNs survive even with large CAG expansions.<\/p>\n

The authors add that the mechanism by which the CAG-CCG LOI modifier influences somatic CAG expansion remains unclear. They also note the need for similar cell-type-specific studies in other repeat expansion disorders that preferentially affect specific neuron populations.<\/p>\n","protected":false},"excerpt":{"rendered":"In a study published in\u00a0Neuron, Chris Kay, PhD, of the University of British Columbia in Vancouver, and colleagues…\n","protected":false},"author":2,"featured_media":647252,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46],"class_list":["post-647251","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/647251","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=647251"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/647251\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/647252"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=647251"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=647251"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=647251"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}