Aviles-Olmos, I; (2013) Exenatide as a Novel Treatment for Parkinson´s Disease. Doctoral thesis , UCL (University College London).

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Abstract

PD is a progressive neurodegenerative disease that results in intolerable disability for most patients despite the best current medical and surgical therapies. A treatment that slows, or stops clinical progression is the major therapeutic goal of current PD research. Multiple avenues of research including epidemiology, molecular genetics and cell biology have identified links between Parkinson’s disease (PD) and Type 2 diabetes mellitus (T2DM). Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism. In parallel with these advances, a treatment for insulin resistance (Exenatide) has been evaluated as a possible disease modifying drug in PD, which forms the core of my PhD. Exenatide is the synthetic version of Exendin-4, confirmed to be an agonist of the Glucagon-like-peptide-1 (GLP-1) receptor, and resistant to the normal GLP-1 enzymatic degradation processes. The aim of this thesis is the evaluation of Exenatide’s possible role as a potential neuroprotective/disease modifying agent in PD (with only preliminary insights regarding its mechanisms of action in neurodegeneration). This study presents the following data: 1. Methods used to obtained proof of concept data from patients with moderate PD treated with Exenatide to provide preliminary support for its further study. 2. An exploration of possible objective measures of differences resulting from Exenatide exposure in a PD biomarker- SPECT imaging, using statistical parametric mapping of a subgroup of patients treated with Exenatide. 3. Prolonged follow up of these patients to further try and help distinguish placebo effects from possible biological effects of Exenatide in PD. 4. An attempt to identify a possible mechanism of action of Exenatide in our cohort of patients. Glucose tolerance tests were performed as an indirect measure of insulin resistance.

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