A collaboration between researchers in China and The University of Iowa (IA, USA) resulted in combining basic molecular biology with big data to investigate the effects of terazosin – a drug typically used to treat enlarged prostate or prostatic hyperplasia – on the progression of Parkinson’s disease (PD).
This study, published in the Journal of Clinical Investigation, followed co-senior author Lei Liu’s (Capital Medical University, Beijing, China) discovery that terazosin can block cell death. This cell-protective activity was reported to be due to the fact terazosin can activate the PGK1 enzyme, which is essential for cellular energy production.
As reduced cellular energy production is a hallmark of PD and energy production declines with age, Liu’s discovery brought the disease into the picture for this research. Furthermore, several inherited forms of PD are caused by genetic defects in cellular energy pathways and drug damage to energy production in neurons.
To investigate the idea of terazosin being able to reduce cell death in PD by increasing cellular energy production, the researchers used numerous different models of PD. They discovered that terazosin prevented neurodegeneration before the onset of cell death. In addition to this, terazosin was demonstrated to slow and stop neurodegeneration even after it started to develop.
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“Current medicines can partially alleviate some of the symptoms of PD, but today we have zero treatments that change the progressive course of this neurodegenerative disease. That’s a terrible state, because as our population ages PD is going to become increasingly common,” commented senior study author, Michael Welsh (The University of Iowa). “I’m really excited about this finding because I think it has the opportunity to change the lives of people with PD – and possibly other types of neurodegenerative disease.”
However, these results gained from animal models may not be able to predict outcomes in humans. Welsh and Nandakumar Narayanan, a neurologist from The University of Iowa, realized that older men were most likely to get PD and take terazosin for enlarged prostate, therefore, clinical databases could hold useful information relating to the effects of terazosin on PD.
The researchers analyzed the Parkinson’s Progression Markers Initiative database and discovered that men with PD who were also taking terazosin had reduced rates of progressive motor disability compared with men who had PD but were not taking the drug.
Though the results seemed promising and the differences discovered between the two groups were reported to be statistically significant, the database examined was small and only 13 men were identified to be taking terazosin. To confirm their findings the team then looked at a larger database called the IBM Watson/Truven Health Analytics MarketScan Database, which included records of over 250 million individuals.
From their data analysis, the researchers discovered that 2880 PD patients taking one of three PGK1-targeting drugs had reduced PD symptoms and complications compared with the 15,409 PD patients not taking such drugs.
Narayanan concluded: “What is particularly exciting is that terazosin is a ‘repurposed drug’. So, we have a lot of safety data already from its clinical use to treat enlarged prostate. We are currently engaged in planning Phase I studies that are funded and we are recruiting patients in Iowa. This is the beginning of what we hope is a sustained and rigorous effort to test this molecule prospectively in order to really determine whether this works.”
Source: University of Iowa Health Care. Big data, bench science suggets drug may slow Parkinson’s progression in people. Press release: www.eurekalert.org/emb_releases/2019-09/uoih-bdb091119.php