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当前和新兴的阿尔茨海默病药物治疗选择:系统评价。

Current and emerging drug treatment options for Alzheimer's disease: a systematic review.

机构信息

Neuropsychopharmacology Research Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

出版信息

Drugs. 2011 Oct 22;71(15):2031-65. doi: 10.2165/11595870-000000000-00000.

Abstract

Alzheimer's disease (AD) is a progressive and ultimately fatal condition that causes debilitating memory loss and extensive deterioration of cognitive and functional abilities. Currently available treatments for AD (donepezil, rivastigmine, galantamine and memantine) are symptomatic and do not decelerate or prevent the progression of the disease. These therapies demonstrate modest, but particularly consistent, benefit for cognition, global status and functional ability. The search for disease-modifying interventions has focused largely on compounds targeting the amyloid-β pathway. To date, the treatments targeting this pathway, such as tramiprosate and semagacestat, have been unsuccessful in demonstrating efficacy in clinical stages of testing. At this point, it is likely that not only amyloid-β aggregation but other possible neuronal mechanisms - such as hyperphosphorylated tau, neuro-inflammation and other processes - play important roles in the pathophysiology of this multifactorial disorder. Development of better disease models and biomarkers is essential for the advancement of knowledge of the disease mechanisms. This systematic review critically examines the efficacy and safety data for currently approved drugs and emerging treatments in AD, as well as discussing the present and future directions of innovation in this field.

摘要

阿尔茨海默病(AD)是一种进行性的、最终致命的疾病,会导致使人衰弱的记忆丧失和认知及功能能力的广泛恶化。目前用于治疗 AD 的方法(多奈哌齐、加兰他敏、利斯的明和美金刚)仅能对症治疗,并不能减缓或阻止疾病的进展。这些疗法在认知、整体状况和功能能力方面表现出适度但特别一致的益处。寻找疾病修饰干预的重点主要集中在针对淀粉样蛋白-β途径的化合物上。迄今为止,针对该途径的治疗方法,如曲美普汀和 semagacestat,在临床试验阶段未能证明其疗效。在这一点上,很可能不仅是淀粉样蛋白-β聚集,还有其他可能的神经元机制,如过度磷酸化的 tau、神经炎症和其他过程,在这种多因素疾病的病理生理学中发挥重要作用。开发更好的疾病模型和生物标志物对于推进对疾病机制的认识至关重要。本系统评价批判性地审查了目前批准的 AD 药物和新兴治疗方法的疗效和安全性数据,并讨论了该领域目前和未来的创新方向。

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