Scott Kurt, Klaus Stephen P
TCD School of Medicine, Trinity College Dublin, Dublin, Ireland.
Department of Neurology, St. James's Hospital, Dublin, Ireland.
Front Neurol. 2024 Aug 6;15:1426075. doi: 10.3389/fneur.2024.1426075. eCollection 2024.
Alzheimer's disease, a progressive neurodegenerative disorder, is marked by beta-amyloid plaque accumulation and cognitive decline. The limited efficacy and significant side effects of anti-amyloid monoclonal antibody therapies have prompted exploration into innovative treatments like focused ultrasound therapy. Focused ultrasound shows promise as a non-invasive technique for disrupting the blood-brain barrier, potentially enhancing drug delivery directly to the brain and improving the penetration of existing therapeutic agents.
This systematic review was conducted using PubMed and Embase databases, focusing on studies published in the last ten years that examined the use of low-intensity focused ultrasound for blood-brain barrier disruption in Alzheimer's disease. The search strategy encompassed terms related to Alzheimer's disease, focused ultrasound, and the blood-brain barrier. Studies were selected based on predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework.
Twelve studies were analyzed, the results of which suggested that low intensity focused ultrasound when combined with microbubbles may safely and transiently disrupt the blood-brain barrier. These studies, primarily early-phase and observational, highlight the potential feasibility of focused ultrasound in facilitating drug delivery to the brain for the treatment of Alzheimer's disease. Notably, one study reported positive impacts on cognitive tests, suggesting potential direct therapeutic effects of focused ultrasound beyond blood-brain barrier disruption.
The results of the included studies indicate the use of focused ultrasound in Alzheimer's disease treatment might be safe and effective in transiently opening the blood-brain barrier. Although current evidence is promising, further research is needed to establish generalizability. Future studies should also aim to further elucidate the mechanisms of action of low-intensity focused ultrasound as well as microbubbles for blood-brain barrier opening and explore potential clinical benefits beyond blood-brain barrier opening such as impacts on cognitive outcomes. Future studies should also aim for greater participant diversity to ensure findings are applicable across the full spectrum of Alzheimer's disease patients.
阿尔茨海默病是一种进行性神经退行性疾病，其特征为β-淀粉样蛋白斑块积累和认知功能下降。抗淀粉样蛋白单克隆抗体疗法疗效有限且副作用显著，这促使人们探索如聚焦超声疗法等创新治疗方法。聚焦超声作为一种非侵入性技术，有望破坏血脑屏障，从而可能增强药物直接向脑内的递送，并提高现有治疗药物的穿透性。
本系统评价使用PubMed和Embase数据库进行，重点关注过去十年发表的研究，这些研究探讨了低强度聚焦超声在阿尔茨海默病中破坏血脑屏障的应用。检索策略涵盖了与阿尔茨海默病、聚焦超声和血脑屏障相关的术语。根据预先定义的纳入和排除标准选择研究。使用牛津循证医学中心证据水平框架评估纳入研究的质量。
分析了12项研究, 结果表明，低强度聚焦超声与微泡联合使用时，可能安全且短暂地破坏血脑屏障。这些研究主要为早期和观察性研究，突出了聚焦超声在促进药物向脑内递送以治疗阿尔茨海默病方面的潜在可行性。值得注意的是，一项研究报告了对认知测试的积极影响，表明聚焦超声除了破坏血脑屏障外，可能还有直接治疗作用。
纳入研究的结果表明，在阿尔茨海默病治疗中使用聚焦超声可能在短暂打开血脑屏障方面是安全有效的。尽管目前的证据很有前景，但仍需要进一步研究以确定其普遍性。未来的研究还应旨在进一步阐明低强度聚焦超声以及微泡打开血脑屏障的作用机制，并探索除打开血脑屏障之外的潜在临床益处，如对认知结果的影响。未来的研究还应以实现更大的参与者多样性为目标，以确保研究结果适用于所有类型的阿尔茨海默病患者。
