This epidemiological, or population, study will use existing medical databases to assess whether three repurposed drugs affect the incidence rate and progression of Parkinson’s.
About the study
Clinical trials are a necessary step in the drug approval process; however, they are often difficult to initiate and manage, whether that be due to cost, patient burden, or other factors. In the instances where clinical trials are not possible, ‘trial emulation’ may offer an alternative. Trial emulation involves performing a randomised trial on an existing medical database to assess the effectiveness of a treatment. For example, researchers could compare the incidence rate of heart disease in patients prescribed a specific high-blood pressure medication compared to those not prescribed to determine if it lowers the risk of heart disease. Although trial emulation can never fully replace clinical trials, it does present a viable approach for collecting real-world data on drug efficacy.
In this study, Professors Li Wei and Tom Foltynie from University College London (UCL), as well as Prof. Anette Shrag from UCL and Prof. Camille Carroll from Newcastle University, will be using trial emulation to investigate three repurposed compounds – istradefylline, montelukast, and ursodeoxycholic acid (UDCA) – as potential disease-modifying treatments for Parkinson’s. Specifically, they will be looking to see whether istradefylline slows Parkinson’s progression and symptoms, and if montelukast and/or UDCA lowers the incidence rate of Parkinson’s in people prescribed those drugs for other conditions.
Trial overview
- Researcher: Professors Li Wei and Tom Foltynie
- Co-PIs: Professors Anette Schrag and Camille Carroll
- Institution: University College London
- Project Type: Other (Epidemiological)
- Status: Ongoing
- Start Date: April 2024
- iLCT-evaluated
- Istradefylline – 2022
- Montelukast – 2021
- UDCA – 2015
More about the study
What are the drugs being evaluated?
Istradefylline
Istradefylline is currently approved in Japan as a companion drug to levodopa to reduce fluctuations in motor symptoms between doses. It belongs to a call of drugs called A2A receptor agonists; these drugs work by blocking the activation of a specific protein (A2A) that plays an important role in initiating inflammation. Chronic neuroinflammation, or inflammation in the brain, is thought to contribute to Parkinson’s progression. Therefore, researchers are interested in whether istradefylline may also slow progression of the condition by reducing inflammation, in addition to its known clinical benefits in stabilizing motor symptoms.
Montelukast
Montelukast belongs to a class of asthma drugs called leukotriene receptor agonists. Leukotriene is a protein that plays a role in promoting inflammation; drugs in this class prevent leukotriene from initiating these pathways, reducing inflammation. Additionally, there is some laboratory evidence to suggest that it may also reduce build-ups of alpha-synuclein – a protein who’s considered to be a driver and hallmark of Parkinson’s.
Montelukast is currently in a phase 2 trial for Parkinson’s in Sweden called the MONTPARK trial. Led by Professor Per Svenningson at the Karolinska Institutet in Stockholm, Sweden, this 18-month study aims to assess whether montelukast can slow the progression of motor symptoms in Parkinson’s. Learn more about this study in a presentation by Prof. Svenningson from our 2024 Spring Update Meeting.
UDCA
Ursodeoxycholic acid (UDCA) is a naturally occurring bile acid which was approved for use in the 1980s to treat gallstones and a rare form of liver disease called primary biliary cirrhosis. Additional research since has shown that UDCA may also have a positive effect on mitochondria – the part of the cell that produces energy. Issues with mitochondria are thought to be a driver of nerve cell (neuron) loss in Parkinson’s; therefore, if UDCA can help restore energy production, it may be able to slow progression.
UDCA has been previously tested in a Cure Parkinson’s supported phase 2 study called the UP-Study. Led by Professor Oliver Bandmann at the University of Sheffield, this study involved 30 people with Parkinson’s taking either UDCA or a placebo for 48 weeks. The results of this trial were published in 2023, with the researchers finding UDCA to be safe and tolerable as well as some evidence towards it improving cellular energy production. Learn more about the results here.
Video presentation – Dr Chengsheng Ju presented a poster on the montelukast portion of this study at one of our Research Update Meetings
Spring Research Update meeting 2024: watch again
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