Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-01-10 DOI:10.1007/s40263-024-01153-5

Vivien Li, Fiona C McKay, David C Tscharke, Corey Smith, Rajiv Khanna, Jeannette Lechner-Scott, William D Rawlinson, Andrew R Lloyd, Bruce V Taylor, Julia M Morahan, Lawrence Steinman, Gavin Giovannoni, Amit Bar-Or, Michael Levy, Natalia Drosu, Andrew Potter, Nigel Caswell, Lynne Smith, Erin C Brady, Bruce Frost, Suzanne Hodgkinson, Todd A Hardy, Simon A Broadley

{"title":"Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.","authors":"Vivien Li, Fiona C McKay, David C Tscharke, Corey Smith, Rajiv Khanna, Jeannette Lechner-Scott, William D Rawlinson, Andrew R Lloyd, Bruce V Taylor, Julia M Morahan, Lawrence Steinman, Gavin Giovannoni, Amit Bar-Or, Michael Levy, Natalia Drosu, Andrew Potter, Nigel Caswell, Lynne Smith, Erin C Brady, Bruce Frost, Suzanne Hodgkinson, Todd A Hardy, Simon A Broadley","doi":"10.1007/s40263-024-01153-5","DOIUrl":null,"url":null,"abstract":"Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.Methods: A list of therapies with anti-EBV effects was developed from existing reviews. A detailed review of pre-clinical and clinical data was undertaken to assess these candidates for potential usefulness and possible harm in MS. A 'drug-CV' and a plain language version focusing on tolerability aspects was created for each candidate. We used validated criteria to score each candidate with an international scientific panel and people living with MS.Results: A preliminary list of 11 drug candidates was generated. Following review by the scientific and lived experience expert panels, six yielded the same highest score. A further review by the expert panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) deemed to have the best balance of efficacy, safety and tolerability for use in MS.Conclusions: Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS.","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4000,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40263-024-01153-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Methods: A list of therapies with anti-EBV effects was developed from existing reviews. A detailed review of pre-clinical and clinical data was undertaken to assess these candidates for potential usefulness and possible harm in MS. A 'drug-CV' and a plain language version focusing on tolerability aspects was created for each candidate. We used validated criteria to score each candidate with an international scientific panel and people living with MS.

Results: A preliminary list of 11 drug candidates was generated. Following review by the scientific and lived experience expert panels, six yielded the same highest score. A further review by the expert panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) deemed to have the best balance of efficacy, safety and tolerability for use in MS.

Conclusions: Scientific and lived experience expert panel review of anti-EBV therapies selected four candidates with evidence for efficacy against EBV and acceptable safety and tolerability for potential use in phase III clinical trials for MS.

查看原文本刊更多论文

重新利用具有抗eb病毒活性的许可药物治疗多发性硬化症：一种系统的方法。

背景：Epstein-Barr病毒（EBV）被认为是多发性硬化症（MS）发展的必要因素，也可能是疾病活动的驱动因素。虽然目前尚不清楚是否持续的病毒复制是多发性硬化症病理的驱动因素，但多发性硬化症研究人员已经考虑了在多发性硬化症治疗中使用对EBV有潜在疗效的药物的前景。我们已经进行了科学和生活经验专家小组评审，以确定现有的可用于多发性硬化症后期临床试验的许可疗法的候选名单。对临床前和临床数据进行了详细的回顾，以评估这些候选药物在ms - A“药物cv”中的潜在有用性和可能的危害，并为每个候选药物创建了一个简单的语言版本，重点关注耐受性方面。我们使用经过验证的标准与国际科学小组和ms患者一起对每个候选药物进行评分。结果：生成了11个候选药物的初步列表。在经过科学和生活经验专家小组的审查后，有六个得出了相同的最高分。专家小组进一步审查了四种药物（famciclovir，替诺福韦alafenamide， maribavir和spironolactone），认为它们在治疗MS的疗效，安全性和耐受性方面具有最佳平衡。结论：科学和生活经验的抗EBV治疗专家小组审查选择了四种具有EBV疗效和可接受的安全性和耐受性的候选药物，用于MS的III期临床试验。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.