The hope and the hype in Parkinson’s disease treatments

Abstract

PD is the most common neurodegenerative movement disorder globally, affecting about 6.1 million individuals globally (2016 published estimates). Unfortunately, there has been no cure for PD till now, and there has been an increasing interest in finding neuroprotective drugs that can slow or stop the progress of the disease. Levodopa is the mainstay of PD treatment, which is transformed to dopamine in the dopamine-producing neurons. However, the efficacy of levodopa is dependent on the survival of the remaining living cells that had not been affected by the disease. Thus, with more disease progression over time, the response to levodopa decreases. As a result, the patient requires adjuvant add-on treatments or non-pharmacological interventions to control PD symptoms and improve their quality of life.
Starting from the basic studies of physiology and pathophysiology of the basal ganglia in medical school, I developed an interest in PD, being a complex neurodegenerative disease. Thus, within the entire six years of my M.B.,B.Ch. studies in the College of Human Medicine, Zagazig University, Egypt (2012-2018), I followed most published clinical studies on PD and systematically studied the candidate treatments for PD.
First, to synthesize evidence on the safety and efficacy of the candidate treatments, we conducted a series of systematic reviews and meta-analyses according to the guidelines of Cochrane Handbook of Systematic Reviews and Meta-analysis, published 2011 and the preferred reporting items of systematic reviews and meta-analysis (PRISMA statement).
Second, we conducted scoping literature reviews for potential agents with no adequate clinical trial data to highlight their potential, rationale, and future directions.
Other primary research works including nationwide profiling of PD patients in Egypt (ClinicalTrials.gov Identifier: NCT02785510; under supervision of Prof. Ali S. Shalash and Prof. Hatem Samir Shehata) and a longitudinal study of 100 PD patients who underwent subthalamic and pallidal DBS in Medical Park Hospital, Istanbul, Turkey (under supervision of Prof. Akin Akakin and Prof. Baran Yilmaz) have also been undertaken within this period but these projects are not discussed in this thesis.
The narrative of this study reflects the unmet needs in different PD stages, starting from early stages where neuroprotective and disease-modifying agents are tested, then mid-stages where most of the patients will require adjuvant/add-on treatments, and later, the advanced stage where pharmacological therapies become insufficient and procedural interventions are attempted to manage the disease.
This study incorporates ten peer-reviewed journal articles and eight abstracts in the world's top Parkinson’s Disease conferences, published since 2015, representing a part of my research portfolio. The published work spans my entire six years of M.B., B.Ch., studies in the medical school of Zagazig University, Egypt.

Date of Award	Sept 2021
Original language	English
Awarding Institution	University of Portsmouth
Supervisor	Matt Parker (Supervisor)