A large observational study carried out by researchers at the University of Iowa, has suggested that a drug used to treat prostate cancer could be repurposed to prevent the development of Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disease that, so far, has no neuroprotective treatments. It is estimated that around 10 million individuals worldwide have Parkinson’s disease, and this number is growing as the population ages. Therapies, such as levodopa and brain stimulation, can improve motor symptoms of Parkinson’s disease, but do not slow the progressive neurodegeneration.
Impaired energy metabolism is a potential and largely unexplored pathogenic factor in Parkinson’s disease. Moreover, age is a major risk factor in Parkinson’s disease, with increased age being associated with impaired cerebral glucose metabolism, reduced mitochondrial biogenesis and lower adenosine triphosphate (ATP) levels. Patients with Parkinson’s disease also present decreased glycolysis and mitochondrial function. Moreover, mitochondrial toxins, such as MPTP and rotenone, have been shown to induce Parkinson’s disease-like phenotypes.
These findings suggest that impaired energy metabolism plays an important role in the pathogenesis of Parkinson’s disease, and therefore therapies that increase energy metabolism and ATP might help prevent the development of Parkinson’s disease.
Terazosin for preventing the development of Parkinson’s disease
Terazosin (TZ) is a drug that is approved for the treatment of prostate cancer, which binds to and increases the activity of phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in glycolysis. TZ crosses the blood-brain barrier, resulting in increased glycolysis and ATP in brain cells.
In this study, the researchers analysed the data from almost 300,000 men from two independent datasets – the Truven Health Analytics MarketScan database in the United States and national health registries in Denmark – to investigate whether the drug can be repurposed to prevent the development of Parkinson’s disease. This study was built on previous preclinical research carried out by the team, which showed that terazosin enhances cellular energy levels and can prevent or slow the progression of Parkinson’s disease in toxin-induced and genetic models of Parkinson’s disease in mice, rats, flies and cells.
Analysis of the data to assess the effectiveness of terazosin for preventing the development of Parkinson’s disease
The researchers used the two databases to identify 150,000 men newly started on terazosin and matched them, based on age and clinical history, to 150,000 men newly started on tamsulosin. The drug tamsulosin is also used to treat prostate cancer, but, unlike terazosin, has no effect on cellular energy. The team then tracked and analysed the data on these men from February 2019 to July 2020 to determine how many patients in each group developed Parkinson’s disease. The researchers found that men taking terazosin were between 12% and 37% less likely to develop Parkinson’s disease during follow-up than men taking tamsulosin. Additionally, the study found that a longer duration of terazosin treatment resulted in an increased protective effect.
Overall, the findings of this study compliment the previous tests carried out in animal models, suggesting that terazosin could be a potential repurposing candidate to prevent the development of Parkinson’s disease in men. Further research, including randomised clinical trials, needs to be done to confirm the neuroprotective effects of terazosin. But this is a promising finding, which suggests that the drug could be used to prevent and not just manage Parkinson’s disease.
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