Vijiaratnam, Nirosen;
(2024)
Exploring biomarkers for parkinsonian diseases and disease modification trials.
Doctoral thesis (Ph.D), UCL (University College London).
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Final PhD thesis Nirosen Vijiaratnam ID 19184922.pdf - Accepted Version Download (2MB) | Preview |
Abstract
Parkinsonian disorders encompass neurodegenerative conditions presenting with similar core clinical motor characteristics that are collectively termed parkinsonism though their associated features and progression vary. Modifying the course of these conditions remains a key goal considering their substantial impact on quality of life and survival. No treatments to date have achieved this. Demonstrating disease modification will require better identification of target populations by reducing cohort heterogeneity with precision approaches as well as selecting cases with maximal neuroprotective potential while also making changes to clinical trial designs and selecting more suitable measures for monitoring disease changes over time and to serve as more suitable endpoints. Quantifiable biomarkers with diagnostic specificity for each parkinsonian disorder that sufficiently predict progression at the time of trial recruitment while also being able to measure disease progression and therapeutic effects of interventions could potentially improve limitations of current trial approaches. Insulin resistance is a characteristic of parkinsonian disorders and pre-clinical and early-stage clinical trials suggest this may be a promising target for achieving disease modification in these conditions. As part of this PhD, I embarked on recruiting and following up patients in clinical trials of Parkinson’s disease and multiple system atrophy exploring the use of the glucagon like peptide-1 receptor agonist exenatide to achieve disease modification. In this thesis I explore biomarkers specific to insulin resistance in addition to more general disease state biomarkers which reflect axonal injury and dopaminergic denervation. I will present the potential for each of these biomarkers to be utilised in future trial analysis by exploring the complexities that can impact on their validity for use. Recommendations will also be proposed for potential future secondary outcome analysis of the current trials as well as overall better approaches for future clinical trial design by incorporation of the biomarkers studied.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Exploring biomarkers for parkinsonian diseases and disease modification trials |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10194970 |
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