GLP-1 Secretion in PD
Research type
Research Study
Full title
Endogenous GLP-1 Secretion in Parkinson’s Disease
IRAS ID
333951
Contact name
Oliver Bandmann
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
3 years, 11 months, 31 days
Research summary
PD is a common brain disease which inevitably gets worse over time. Our current limited understanding of mechanisms leading to PD, combined with the lack of disease-modifying treatment which would slow down disease progression or even halt it, will therefore lead to ever increasing human suffering and considerable socioeconomic strain. There is strong evidence of a link between the gut and brain in PD. However, the precise nature of this link remains uncertain. Many studies have shown changes in the gut microbiota (GM) composition in PD, but it is not clear whether or how these GM alterations may cause PD. GM changes may already be present in pre-motor PD, further supporting an important role of the GM in the development of PD. GM changes and its associated bile acid (BA) metabolising functions significantly change BA signatures in the host gut and in other tissues including the brain. BA metabolism is markedly impaired in PD. However, the functional relevance of BA metabolism in PD is still poorly understood.
Altered concentrations of BA and other metabolites of the GM, in particular short chain fatty acids (SCFA) in the gut play a key role in the regulation of GLP-1 secretion. GLP-1 enhances insulin production and secretion. Insulin signalling promotes neuronal cell survival via different mechanisms. GLP-1 receptor agonists such as exenatide have considerable potential to slow down the progression of PD.
UDCA treatment results in increased GLP-1 secretion in model systems, healthy controls and patients with other diseases. The aim of this study is to explore whether GLP-1 release is impaired in patients with PD compared to age- and sex-matched controls. We want to determine whether brief treatment with UDCA can restore the GLP-1 profile in PD and determine the underlying mechanisms.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
24/EE/0006
Date of REC Opinion
13 Feb 2024
REC opinion
Further Information Favourable Opinion