Collaborating researchers at the University of Iowa and Capital Medical University in Beijing, China, found that a drug used to treat enlarged prostate, terazosin, appears able to slow the progress of Parkinson’s disease.
Collaborating researchers at the University of Iowa and Capital Medical University in Beijing, China, found that a drug used to treat enlarged prostate, terazosin, appears able to slow the progress of Parkinson’s disease. The research was published in The Journal of Clinical Investigation.
Terazosin is also used to high blood pressure. Lei Liu, co-senior study author, with Capital Medical University, found that terazosin, typically used to treat benign prostatic hyperplasia, or enlarged prostate, could also block cell death. This was related to the drug’s activation of an enzyme called PGK1, which is essential for the production of cellular energy.
Decreased cellular energy production is a major hallmark of Parkinson’s disease. Energy production decreases with age, which is a primary risk factor for Parkinson’s. Also, there are several inherited forms of Parkinson’s that are sparked by genetic mutations in cellular energy pathways. Also, some drugs that cause Parkinson’s do so by damaging neurons’ energy production.
This led the researchers to test terazosin’s ability to increase energy production in cells in hopes it might decrease cell death in Parkinson’s. They found that the drug prevented neurodegeneration if given before cell death, but also slowed or stopped neurodegeneration even if neurodegeneration had started.
“Current medicines can partially alleviate some of the symptoms of Parkinson’s disease,” stated senior study author Michael Welsh, University of Iowa professor of internal medicine, a Howard Hughes Medical Institute investigator, and director of the Pappajohn Biomedical Institute at the UI. “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 Parkinson’s disease is going to become increasingly common. I’m really excited about this finding because I think it has the opportunity to change the lives of people with Parkinson’s disease (and possibly other types of neurodegenerative disease.”)
Liu, who received his doctorate in 2002 from UI working with Welsh, said, “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.”
To test the theory in humans, they turned to Nandakumar Narayanan, a UI neurologist who treats and researches Parkinson’s. Because there was an overlap in patient populations—older men are more likely to receive treatment for enlarged prostate and Parkinson’s disease—they were able, along with Jordan Schultz, UI assistant professor of psychiatry, evaluated the Parkinson’s Progression Markers Initiative (PPMI) database, which is sponsored by The Michael J. Fox Foundation for Parkinson’s Research.
They found that men with Parkinson’s who took terazosin had slower progression of motor disability compared to the Parkinson’s patients who took a different drug, tamsulosin, for enlarged prostate. Tamsulosin (Flomax) is used to treat enlarged prostate but doesn’t have the same effect on the PGK1 enzyme that terazosin does.
Although the research was promising, the PPMI database is small, and only 13 men were found in it who were taking terazosin or similar drugs that activate the PGK1 enzyme, compared to 293 men with Parkinson’s who were on tamsulosin or not taking of these drugs. The difference in motor decline in the two groups was statistically significant, but required confirmation using a large dataset, such as the IBM Watson/Truven Health Analytics MarketScan Database, which has de-identified health records of more than 250 million people.
So the researchers collaborated with Jacob Simmering and Philip Polgreen, both at UI. They isolated 2,880 Parkinson’s patients taking one of the three drugs that target PGK1 and a comparison group of 15,409 Parkinson’s patients taking tamsulosin. By tracking ICD-9/ICD-10 medical codes, they found that terazosin and similar drugs seem to decrease the symptoms and complications of Parkinson’s disease.
“What is particularly exciting is that terazosin is a ‘repurposed drug,’” said Narayanan. “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.”
