{"title":"Tofersen 用于 SOD1 ALS。","authors":"William H Everett, Robert C Bucelli","doi":"10.1080/17582024.2024.2402216","DOIUrl":null,"url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in <i>SOD1</i> make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of <i>SOD1</i> mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.</p>","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"149-160"},"PeriodicalIF":2.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524200/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tofersen for SOD1 ALS.\",\"authors\":\"William H Everett, Robert C Bucelli\",\"doi\":\"10.1080/17582024.2024.2402216\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in <i>SOD1</i> make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of <i>SOD1</i> mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.</p>\",\"PeriodicalId\":19114,\"journal\":{\"name\":\"Neurodegenerative disease management\",\"volume\":\" \",\"pages\":\"149-160\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524200/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurodegenerative disease management\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17582024.2024.2402216\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurodegenerative disease management","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17582024.2024.2402216","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/27 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
肌萎缩性脊髓侧索硬化症(ALS)是一种影响运动系统的神经退行性疾病。ALS 的异质性使试验设计变得复杂。ALS 的遗传形式为在异质性较低的人群中进行干预提供了机会。肌萎缩性脊髓侧索硬化症与 SOD1 的功能增益突变有关,因此 "基因敲除 "策略是一种很有吸引力的治疗方法。Tofersen是一种反义寡核苷酸,可通过RNA酶介导的SOD1 mRNA降解减少SOD1的表达。虽然托非森的 III 期试验未能达到主要终点,但开放标签扩展数据表明,托非森可延缓 SOD1 ALS 的进展。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in SOD1 make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of SOD1 mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.