The goal of this preclinical study was to determine whether two anti-gout medications could slow progression in models of Parkinson’s.
About the study
Professor Heather Mortiboys at the University of Sheffield conducted an 18-month preclinical study on two anti-gout medications – probenecid and thiosalicylic acid – to determine their potential as disease-modifying treatments for Parkinson’s. Gout is a type of inflammatory arthritis suggested to have an association with Parkinson’s risk. In prior preclinical screenings, these two drugs showed strong evidence of being able to restore the health of mitochondria – the part of the cell involved with energy production. Issues with the mitochondria are common in the nerve cells (neurons) of people with Parkinson’s and is thought to be a driver of progression.
The primary goal of this project was to better understand the mechanism of action of these drugs, or what they interact with in the cell to achieve their intended effect. They also looked for evidence of neuroprotection and target engagement. We are currently waiting on the publication of results of this study.
Trial overview
- Researcher: Professor Heather Mortiboys
- Institution: University of Sheffield
- Project Type: Preclinical
- Status: Completed
- Start Date: May 2023
- Therapy Target: Mitochondrial dysfunction
More about the study
How could probenecid and thiosalicyclic acid help fix mitochondria?
An important aspect of maintaining the health of mitochondria is ensuring that old or damaged mitochondria are recycled. The process of breaking down and recycling mitochondria is called mitophagy. This process is important not only because it helps regulate energy production in the cell, but it also helps prevent build-up of toxic molecules called Reactive Oxygen Species (ROS). Accumulation of ROS can cause oxidative stress and even cell death.
There is already evidence of reduced mitophagy activity in people with Parkinson’s, especially those with specific genetic variations. Those who carry PRKN and/or PINK1 mutations – two genetic risk factors for Parkinson’s – often have problems with mitophagy as the proteins these genes code for (Parkin and PINK1) regulate one of the cell’s mitophagy pathways. Probenicid and thiosalicyclic acid are thought to act on a “Parkin-independent pathway”, meaning the effectiveness of these drugs is not influenced by the prescence of PRKN/PINK1 variations.
A review of our 2023 preclinical projects
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