The Future of Parkinson’s Treatment – Personalised and Precision Medicine

Abstract

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. KeywordsParkinson's disease, non-motor symptoms, quality of life, personalised medicine, precision medicine Disclosure: Nataliya Titova, 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. 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][4][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 alg...

‘Levodopa Phobia’: a review of a not uncommon and consequential phenomenon

“…12–14 The latter strategy is one of the ‘personality enablers’ of the recently described ‘circle of personalised medicine’ for PD. 13,14 In selected cases, use of objective measures such as digital monitoring (wearable devices highlighting bradykinesia, Case 2) or Datscan (as in Case 1) may be helpful in convincing unwilling phobic PD patients to realise the extent of parkinsonism and the need to start levodopa therapy. Input from an expert patient group is also useful for convincing the patient regarding the benefits of levodopa therapy as is the role of a skilled psychotherapist with expertise in treating anxiety phenomena.…”

Non‐motor Parkinson disease: new concepts and personalised management

“…Personalised medicine is the modern way of delivering an individualised holistic PD treatment strategy 9 , 52 . Personalised medicine thus encompasses several strands of treatment known as the enablers.…”

A noninterventional study evaluating the effectiveness of rotigotine and levodopa combination therapy in younger versus older patients with Parkinson’s disease

“…Administering low April 2018 doses of levodopa and DAs may further reduce the likelihood of other complications of chronic dopamine replacement therapy, such as impulse control disorders or dopamine dysregulation syndrome [11,12]. Personalized medicine is particularly relevant for the treatment of PD, with important considerations including patient age, comorbidities, and lifestyle [13]. PD primarily affects older patients (>60 years) [14], and as life expectancy in patients with PD has increased, patients are treated for longer, leading to more treatment options .…”

“…PD primarily affects older patients (>60 years) [14], and as life expectancy in patients with PD has increased, patients are treated for longer, leading to more treatment options . As such, many current PD treatment guidelines may not be valid for PD patients with 'healthy ageing' [13]. Due to increasing patient longevity, the previously mentioned issues linked to chronic levodopa exposure are also pertinent [15].…”