A drug used to treat an enlarged prostate and high blood pressure, terazosin, has been shown to slow the progression of Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disease that affects mobility and mental ability through progressive damage to the substantia nigra region of the brain. The disease is common and while not fatal, complications can reduce life expectancy. Around 1 in 500 people suffer from the disease. While there are drugs that can be provided to patients to help ease the symptoms, there is no cure for the disease.
Terazosin is most commonly used to treat benign prostatic hyperplasia but it also appears to block cell death associated with Parkinson’s disease, according to a study conducted by a team of researchers from the University of Iowa and Capital Medical University in Beijing.
As people age, cellular energy production decreases, but this is accelerated in patients with Parkinson’s disease. Certain forms of Parkinson’s disease are caused by mutations in cellular energy pathways and drugs that cause Parkinson’s disease do so through the disruption of cellular energy production in neurons.
Terazosin activates an enzyme called PGK1 which is required by cells to produce energy. The researchers hypothesized that the drug could potentially be used to increase energy production and thus slow the progression of the disease.
The researchers demonstrated that treatment with terazosin prevented neurodegeneration if administered before cell death had occurred and slowed, or in some cases stopped, neurodegeneration once it had started.
“When we tested the drug in various different animal models of PD, they all got better. Both the molecular changes in the brain associated with cell death and the motor coordination in the animals improved,” said Lei Liu, co-senior study author.
The researchers also studied the effects of the drug on patients through an analysis of the Parkinson’s Progression Markers Initiative (PPMI) database. Since the drug is already prescribed to patients to treat an enlarged prostate – most common in older men – it was possible to study its effects on the progression of Parkinson’s disease. The researchers compared data from PD patients with an enlarged prostate and compared how the disease progressed against patients who had been provided with a different prostate-shrinking drug, tamsulosin, which does not have the same effect on PGK1.
The researchers found that Parkinson’s disease progression was slower in patients who had been prescribed terazosin than patients who were treated with tamsulosin. While the results of the study were promising, the PPMI database only included data for 13 men who had received drugs that activated the PGK1 enzyme compared to 293 men who had been treated with tamsulosin.
The researchers then used the IBM Watson/Truven Health Analytics MarketScan Database and identified a further 2,880 patients with Parkinson’s disease on one of three drugs that targeted PGK1 and 15,409 patients taking tamsulosin. They found the PGK1 activating drugs all decreased symptoms and complications of Parkinson’s disease.
The researchers are now planning a Phase 1 study and have already started recruiting patients for a clinical trial using the drug.
The study is detailed in the paper – Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases – which was recently published in The Journal of Clinical Investigation. DOI: 10.1172/JCI129987