Rafii Michael S, Aisen Paul S
Department of Neurosciences, University of California-San Diego, Gilman Drive M/C 0949, La Jolla, CA 92093, USA.
BMC Med. 2009 Feb 19;7:7. doi: 10.1186/1741-7015-7-7.
Alzheimer's disease is a devastating neurological disorder that affects more than 37 million people worldwide. The economic burden of Alzheimer's disease is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least $100 billion. Current FDA-approved drugs for Alzheimer's disease do not prevent or reverse the disease, and provide only modest symptomatic benefits. Driven by the clear unmet medical need and a growing understanding of the molecular pathophysiology of Alzheimer's disease, the number of agents in development has increased dramatically in recent years. Truly *'disease-modifying' therapies that target the underlying mechanisms of Alzheimer's disease have now reached late stages of human clinical trials. Primary targets include beta-amyloid, whose presence and accumulation in the brain is thought to contribute to the development of Alzheimer's disease, and tau protein which, when hyperphosphorylated, results in the self-assembly of tangles of paired helical filaments also believed to be involved in the pathogenesis of Alzheimer's disease. In this review, we briefly discuss the current status of Alzheimer's disease therapies under study, as well the scientific context in which they have been developed.
阿尔茨海默病是一种极具破坏性的神经疾病,全球有超过3700万人受其影响。阿尔茨海默病的经济负担极为沉重;仅在美国,每年用于患者护理的直接和间接费用估计至少达1000亿美元。目前美国食品药品监督管理局(FDA)批准用于治疗阿尔茨海默病的药物既不能预防也无法逆转该疾病,仅能提供有限的症状缓解。由于明确的未满足医疗需求以及对阿尔茨海默病分子病理生理学的日益了解,近年来正在研发的药物数量急剧增加。真正针对阿尔茨海默病潜在机制的“疾病修饰”疗法现已进入人体临床试验后期阶段。主要靶点包括β-淀粉样蛋白,其在大脑中的存在和积累被认为与阿尔茨海默病的发展有关,以及tau蛋白,当tau蛋白过度磷酸化时,会导致成对螺旋丝缠结的自我组装,这也被认为与阿尔茨海默病的发病机制有关。在本综述中,我们简要讨论了正在研究的阿尔茨海默病疗法的现状以及它们研发的科学背景。