估计有650万65岁或以上的美国人患有阿尔茨海默病(AD)。到2060年将增长到1380万美国人。尽管痴呆症的负担越来越大,在超过20年的时间里,AD的药物开发没有根本变化。目前批准的用于AD的药物仅产生适度的认知症状改善,具有小的效应大小。在迫切需要开发用于有症状的AD的有效药物与在很大程度上失败的疾病修饰搜索之间存在越来越多的不匹配。AD临床试验的失败率总体较高,特别是用于疾病改善疗法。AD的研究工作主要集中在淀粉样蛋白-β和tau病理上,但是将临床研究限制在这种疾病的这些“经典标志”上并不能解决最紧急的患者,看护人,或社会需要。相反,临床研究应考虑AD的复杂病理生理学。需要创新的方法来提供开箱即用的思维,重新想象试验设计,干预措施,和结果以及蛋白质组学和液体生物标志物分析的进展,用于诊断和疾病监测。一种新方法提供了一种非常具体的,然而,对HGF/MET神经营养系统产生正调节的多管齐下干预目前正在中晚期临床试验中对轻度至中度AD进行测试.来自这些试验的结果可以提供数据来支持用于开发用于治疗各种疾病阶段的AD的创新药物的新方法,并且可以为AD和其他神经退行性疾病中已经有症状和疾病改变的那些提供益处。
An estimated 6.5 million Americans aged 65 years or older have Alzheimer\'s disease (AD), which will grow to 13.8 million Americans by 2060. Despite the growing burden of dementia, no fundamental change in drug development for AD has been seen in > 20 years. Currently approved drugs for AD produce only modest symptomatic improvements in cognition with small effect sizes. A growing mismatch exists between the urgent need to develop effective drugs for symptomatic AD and the largely failed search for disease modification. The failure rate of clinical trials in AD is high overall, and in particular for disease-modifying therapies. Research efforts in AD have focused predominantly on amyloid-β and tau pathologies, but limiting clinical research to these \"classical hallmarks\" of the disease does not address the most urgent patient, caregiver, or societal needs. Rather, clinical research should consider the complex pathophysiology of AD. Innovative approaches are needed that provide outside-the-box thinking, and re-imagine trial design, interventions, and outcomes as well as progress in proteomics and fluid biomarker analytics for both diagnostics and disease monitoring. A new approach offering a highly specific, yet multi-pronged intervention that exerts positive modulation on the HGF/MET neurotrophic system is currently being tested in mid-to-late-stage clinical trials in mild to moderate AD. Findings from such trials may provide data to support novel approaches for development of innovative drugs for treating AD at various disease stages, including among patients already symptomatic, and may offer benefits for other neurodegenerative diseases.