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Editorial Parkinson’s Disease The Future of Parkinson’s Treatment – Personalised and Precision Medicine Nataliya Titova, 1 Peter Jenner 2 and K Ray Chaudhuri 3,4 1. 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; 2. Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King’s College London, UK; 3. National Parkinson Foundation International Centre of Excellence, King’s College London and King’s College Hospital, London, UK; 4. Maurice Wohl Clinical Neuroscience Institute, King’s College London, UK T he modern concept of Parkinson’s disease (PD) has changed and evolved and we consider Parkinson’s to be a multi-neurotransmitter dysfunction-related disorder with central and peripheral nervous system involvement. The clinical expression is thus a mixture of the outwardly evident motor symptoms and a range of ‘hidden’ non-motor symptoms. The complex underlying neuropathology of PD calls for a reassessment of the treatment strategies currently used. Treatment of PD is guideline-driven and in most cases based on a dopamine replacement strategy or surgical manipulation of brain dopaminergic pathways. Treatment of many non-dopaminergic non-motor and some motor symptoms, which have major effects on quality of life, continue to remain a key unmet need. Like in other chronic conditions such as rheumatology, the role of personalised medicine in PD needs to be increasingly considered. Personalised medicine for PD is not just a genetic approach to treatment but encompasses various strands of treatment. These include pharmacogenetic, pharmacological, as well as socio-demographic and lifestyle-related issues. Once these ‘enablers’ of personalised medicine are considered then satisfactory treatment for our patients with Parkinson’s can be achieved in an individualised manner. Future therapy for PD should move in that direction. Keywords Parkinson’s disease, non-motor symptoms, quality of life, personalised medicine, precision medicine Disclosure: Nataliya Titiva, Peter Jenner and K Ray Chaudhuri have nothing to declare in relation to this article. This article is a short opinion piece and has not been submitted to external peer reviewers. No funding was received for the publication of this article. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 11 April 2017 Published Online: 8 May 2017 Citation: European Neurological Review, 2017;12(1):15–6 Corresponding Author: K Ray Chaudhuri, Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, King’s College London, Cutcombe Road, SE5 9RT, London. E: ray.chaudhuri@nhs.net Levodopa therapy and other dopamine replacement therapies (DRTs) have remained the cornerstone for the treatment of Parkinson’s disease (PD) since the 1960s. 1 Many motor symptoms of PD can be partially reversed by DRT as well as more invasive therapies such as deep brain stimulation (DBS) of the subthalamic nucleus. However, many challenges remain both in the short and long term. Largely, these relate to the fact that the modern definition of PD has changed and the condition is now regarded as a complex disease with syndromic presentations manifesting as non-motor subtypes. 2,3 Non-dopaminergic presentations, such as cholinergic, serotonergic and noradrenergic, can dominate the clinical phenotype of PD and form the basis of the recently described non-motor subtypes of PD. 3–5 This heterogeneity of neuropathology and diversity of presentation needs treatment tailored to suit the clinical phenotypes. However, globally PD still continues to be treated by guideline-based algorithms underpinned by generic prescribing of levodopa and other DRTs. New drugs continue to be focussed on single targets when PD is known to be a multi-system, -neurotransmitter and -dysfunction-related disorder. Clearly, in future, this approach needs to change and the concept of a holistic personalised medicine strategy combining several strands of genetic, therapeutic, personal and socio-economic variables needs to be embraced. 6,7 Personalised medicine The concept of personalised medicine is subject to interpretation. The American Medical Association defines this ‘as each person’s unique clinical, genetic and environmental information’ while others consider personalised medicine purely from a genetic or pharmacogenetic ‘precision’ therapy standpoint. 8 A more recent concept of the components that make up personalised medicine in PD as described recently by Titova and Chaudhuri is explained in Table 1. 7 The concept of personalised medicine is particularly relevant for PD, a condition with multiple pathology and neurotransmitter-linked syndromes. 2,3 For the development of new drugs relevant to the delivery of personalised medicine, robust animal models of PD are required. These models need to reflect the progressive pathology and multineurotransmitter defects that characterise PD. Such models based on toxin and/or genetic manipulation of rodents and primates remain elusive and represent an under-researched but key unmet need for the future of PD. Preliminary ‘bench’-based work has unravelled new potential targets for therapy which may help with aspects of non-motor symptoms (sleep dysfunction, cognition, pain and autonomic dysfunction) in PD, as well as some motor symptoms (gait freezing, dyskinesias). A combination of good animal model coupled with multiple non-dopaminergic target-based TOU CH MED ICA L MEDIA 15