Personalized Medicine and Nonmotor Symptoms in Parkinson's Disease

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.