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重新利用对爱泼斯坦-巴尔病毒有活性的已获许可药物治疗多发性硬化症:一种系统方法。

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

作者信息

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

机构信息

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3010, Australia.

Multiple Sclerosis Australia, Suite 3.01 18 Flour Mill Way, Summer Hill, NSW, 2130, Australia.

出版信息

CNS Drugs. 2025 Mar;39(3):305-320. doi: 10.1007/s40263-024-01153-5. Epub 2025 Jan 10.

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.

摘要

背景

爱泼斯坦-巴尔病毒(EBV)被认为是多发性硬化症(MS)发病的必要因素,也可能是疾病活动的驱动因素。尽管尚不清楚持续的病毒复制是否是MS病理的驱动因素,但MS研究人员已考虑使用对EBV可能有效的药物来治疗MS。我们进行了科学和生活经验专家小组评审,以筛选出可用于MS后期临床试验的现有许可疗法。

方法

根据现有综述制定了具有抗EBV作用的疗法清单。对临床前和临床数据进行了详细审查,以评估这些候选药物在MS中的潜在用途和可能的危害。为每个候选药物创建了一份“药物简历”和一个侧重于耐受性方面的通俗易懂版本。我们使用经过验证的标准,由一个国际科学小组和MS患者对每个候选药物进行评分。

结果

生成了一份11种候选药物的初步清单。经过科学和生活经验专家小组的评审,六种药物获得了相同的最高分。专家小组的进一步评审筛选出了四种药物(泛昔洛韦、丙酚替诺福韦、马立巴韦和螺内酯),认为它们在MS治疗中疗效、安全性和耐受性的平衡最佳。

结论

对抗EBV疗法的科学和生活经验专家小组评审选出了四种对EBV有疗效证据、安全性和耐受性可接受的候选药物,可用于MS的III期临床试验。

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