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UK funding (£593,427): Investigating the mechanisms of synaptic dysfunction in genetic models of Parkinson's Ukri1 Feb 2025 UK Research and Innovation, United Kingdom
Overview
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Investigating the mechanisms of synaptic dysfunction in genetic models of Parkinson's
| Abstract | Parkinson's (PD) is set to become the most common brain disorder worldwide by 2040. However, there is still no definitive long term treatment with the best therapeutic only working for a short period of time, and tied with the possibility of causing its own side effects with extended use. Getting involved early in treatment has been proven to improve the quality of life for patients and helps manage the symptoms over time. To make progress in finding new treatments, we need to understand how the disease progresses and what goes wrong at each stage. We're particularly interested in finding early signs of Parkinson's and understanding what causes them. My initial UKRI future leader fellowship supported the first of a four-phase comprehensive plan designed to better understand and treat PD: Phase 1: Identifying the different features of Parkinson's at various points in time. Phase 2: Finding specific targets that can be used to slow down or reduce the impact of these disease features. Phase 3: Modifying these features by targeting the identified areas at specific times. Phase 4: Developing new compounds and testing them in clinical trials. We've already discovered that the electrical activity in neurons derived from stem cells (iPSC) from people with PD is different from healthy neurons. We've also noticed that behaviour related to PD, like anxiety and problems with thinking, can change depending on factors like sex, age and genetics and can actually show up at an early stage. The original UKRI-FLF funding was integral to these findings which has led us towards completion of Phase 1. Here, I propose work for Phase 2. In this renewal, we're trying to find targets that can help lessen the impact of Parkinson's disease. To figure out why these changes happen, my aims for this UKRI-FLF renewal/Phase 2 are: 1. Record the electrical activity in iPSC stem cells to see if there are broad patterns in how ion channels (which control electrical activity) are behaving. 2. Use compounds and a special technique (PatchSeq) to pinpoint exactly which parts of the ion channels are causing the problems. 3. Test these changes in a controlled environment to see if they affect the firing of neurons. 4. Study how the brain's activity changes in PD mice and brain slices to understand the relevant impact on PD related symptoms. The data we have gathered so far using the UKRI FLF has been pivotal in enabling me to successfully apply for further funding to expand the programme into phases 2 and 3 (specifically I have won and been awarded grants from Parkinson's UK and the Moondance Foundation). However, the UKRI FLF renewal will support the core research needed to achieve the aims of phase 2 and catalyse the programme as a whole. By doing this research, we are on the way to finding potential routes to modify the disease features, taking us one step closer to developing effective long-term treatments. |
| Category | Fellowship |
| Reference | MR/Y03404X/1 |
| Status | Active |
| Funded period start | 01/02/2025 |
| Funded period end | 31/01/2028 |
| Funded value | £593,427.00 |
| Source | https://gtr.ukri.org/projects?ref=MR%2FY03404X%2F1 |
Participating Organisations
| CARDIFF UNIVERSITY | |
| Astrazeneca | |
| King's College London |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: Cardiff University, Cardiff.
