Hampel H, O'Bryant S E, Durrleman S, Younesi E, Rojkova K, Escott-Price V, Corvol J-C, Broich K, Dubois B, Lista S
a AXA Research Fund & UPMC Chair , Paris , France.
b Département de Neurologie , Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
Climacteric. 2017 Apr;20(2):107-118. doi: 10.1080/13697137.2017.1287866. Epub 2017 Feb 9.
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.
经过深入的科学探索以及十多年的失败试验，阿尔茨海默病（AD）仍然是一种致命的全球流行病。传统的研究和药物开发模式继续以单一的“神奇子弹”药物针对临床表型各异的晚期患者。在此，我们提出，现在是时候进行范式转变，转向实施精准医学（PM），以加强对AD的风险筛查、检测、治疗和预防。通过融合大数据科学、系统生物学、基因组测序、血液生物标志物、综合疾病建模和4P医学等突破性技术进展，将提供实现AD精准医学的总体架构。据推测，将AD解构为该异质目标人群中存在的多个遗传和生物学亚组，将为根据个体特定的生物学构成，用可能最有效的特定药物治疗个体患者提供有效的精准医学策略。阿尔茨海默病精准医学倡议（APMI）是由顶尖跨学科临床医生和科学家开展的国际合作项目，致力于在神经病学、精神病学和神经科学领域实施精准医学。据推测，在AD和其他神经退行性疾病中成功实现精准医学将带来突破性疗法，例如在肿瘤学中那样，具有优化的安全性、更高的有效率和更好的治疗反应，特别是通过生物标志物引导的临床前疾病早期阶段临床试验。
