Titova Nataliya, Chaudhuri K Ray
Federal State Budgetary Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
National Parkinson Foundation International Centre of Excellence, King's College London and King's College Hospital and The Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom.
Int Rev Neurobiol. 2017;134:1257-1281. doi: 10.1016/bs.irn.2017.05.015.
Parkinson's disease (PD) is a multineurotransmitter dysfunction related disorder resulting in a range of motor and nonmotor symptoms. Phenotypic heterogeneity is pronounced in PD and nonmotor symptoms dominant subtypes have been described. These endophenotypes may be underpinned by considerable nondopaminergic dysfunction; however, conventional treatment of PD continues to be mostly reliant on dopamine replacement strategy or manipulation of brain dopaminergic pathways. Consequently, treatment of many nondopaminergic nonmotor and some motor symptoms remains a key unmet need. It is also recognized that treatment strategies for PD are influenced by a number of nondrug-related issues. These include factors such as age, personality, and preferences for treatment, cultural beliefs, lifestyle, pharmacoeconomics, pharmacogenetics as well as comorbidity. Therefore, the success of clinical therapy will rest on how much these factors are considered to develop a truly holistic treatment plan. Personalized medicine is the modern way of delivering this holistic strategy for treatment of PD. Personalized medicine thus encompasses several strands of treatment. From the pharmaceutical point of view, it should involve dopaminergic and nondopaminergic strategies. In addition, there are substrategies involving precision and tailored medicine to suit the needs and requirements of individual patients. Precision medicine would be relevant for patients who may be at risk of developing the clinical syndrome of Parkinson's as identified by specific gene mutations. Precision medicine in this scenario will attempt to be preventive. Tailored medicine would address the "single multifactorial" complex nature of PD and address symptoms as well subtype-specific strategies. Personalized medicine is now practiced for other conditions such as oncology as well as diabetes. In this chapter, we discuss the rationale and the need to develop strategies for personalized medicine for PD.
帕金森病（PD）是一种与多神经递质功能障碍相关的疾病，会导致一系列运动和非运动症状。PD的表型异质性很明显，并且已经描述了以非运动症状为主的亚型。这些内表型可能由相当程度的非多巴胺能功能障碍所支撑；然而，PD的传统治疗仍然主要依赖于多巴胺替代策略或对脑多巴胺能通路的调控。因此，许多非多巴胺能非运动症状和一些运动症状的治疗仍然是一个关键的未满足需求。人们也认识到，PD的治疗策略受到许多与药物无关的问题的影响。这些因素包括年龄、个性、治疗偏好、文化信仰、生活方式、药物经济学、药物遗传学以及合并症等。因此，临床治疗的成功将取决于在制定真正全面的治疗计划时对这些因素的考虑程度。个性化医疗是实施这种全面的PD治疗策略的现代方式。个性化医疗因此涵盖了多个治疗方面。从药物治疗的角度来看，它应该包括多巴胺能和非多巴胺能策略。此外，还有涉及精准医学和量身定制医学的子策略，以满足个体患者的需求。精准医学适用于那些可能因特定基因突变而有患帕金森临床综合征风险的患者。在这种情况下，精准医学将试图起到预防作用。量身定制医学将解决PD的“单一多因素”复杂性质，并针对症状以及亚型特异性策略。个性化医疗现在也应用于肿瘤学和糖尿病等其他疾病。在本章中，我们将讨论为PD制定个性化医疗策略的基本原理和必要性。
