Emily Francis, Samantha Paylor, Cindy Van, Bindu Mathews, Millad J Sobhanian, Daniel Z Mansour, George Hennawi, Nicole J Brandt
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引用次数: 0
Abstract
Introduction: Alzheimer's disease (AD) remains a major public health challenge, with growing prevalence and limited treatment options that modify disease progression. Recent advances have led to the development and approval of Anti-amyloid-β (Aβ) monoclonal antibodies, which represent a paradigm shift from symptomatic management to targeted disease modification.
Areas ccovered: Agents such as lecanemab and donanemab selectively bind aggregated forms of Aβ and have demonstrated modest but statistically significant slowing of cognitive and functional decline in early AD. However, these therapies are associated with amyloid-related imaging abnormalities (ARIA), particularly in individuals carrying the APOE ε4 allele, necessitating close monitoring and individualized risk assessment. Implementation challenges, including high treatment burden, cost, and real-world applicability, have limited broad clinical adoption. This review examines the mechanistic differences, clinical trial outcomes, and safety considerations of Aβ monoclonal antibodies, while also highlighting emerging therapies and the need for inclusive, precision-guided approaches.
Expert opinion: As research continues to evolve, balancing clinical benefits with safety and accessibility will be critical in defining the role of anti-amyloid-β therapies within the broader landscape of AD care.
阿尔茨海默病(AD)仍然是一项重大的公共卫生挑战,其患病率不断上升,但改变疾病进展的治疗选择有限。最近的进展导致了抗淀粉样蛋白-β (a β)单克隆抗体的开发和批准,这代表了从症状管理到靶向疾病修饰的范式转变。研究领域:lecanemab和donanemab等药物选择性结合Aβ聚集形式,并显示出适度但统计学上显著的早期AD认知和功能衰退减缓。然而,这些疗法与淀粉样蛋白相关成像异常(ARIA)有关,特别是在携带APOE ε4等位基因的个体中,需要密切监测和个体化风险评估。实施方面的挑战,包括高昂的治疗负担、成本和现实世界的适用性,限制了广泛的临床应用。本文综述了Aβ单克隆抗体的机制差异、临床试验结果和安全性考虑,同时也强调了新兴疗法和对包容性、精确指导方法的需求。专家意见:随着研究的不断发展,平衡临床获益与安全性和可及性将是确定抗淀粉样蛋白疗法在阿尔茨海默病治疗的更广泛领域中的作用的关键。
期刊介绍:
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.