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Could prostate drugs reduce Parkinsons disease risk?

A new study suggests that repurposing glycolysis-enhancing drugs such as terazosin, which is typically used to treat an enlarged prostate, may reduce the risk of Parkinson’s disease in men.

Parkinson’s disease is a neurodegenerative disorder caused by reduced levels of a brain chemical called dopamine. The symptoms worsen over time, and the disease can have a wide range of complications, from causing difficulty speaking to difficulty chewing and swallowing.

While Parkinson’s disease primarily affects movement, dopamine loss can also cause nonmotor symptoms, including depression, dementia, trouble sleeping, and low energy.

Various treatments can address the broad spectrum of symptoms, but currently, no medication can cure Parkinson’s disease.

A majority of treatments focus on restoring dopamine levels. Recently, however, more research has investigated ways to increase energy levels using a metabolic pathway called glycolysis.

All cells need energy to carry out their functions, and glycolysis is one of the first metabolic pathways in the production of energy.

This multistep pathway breaks down glucose into different types of molecules used for further energy production.

The findings of a 2014 study suggest that increased oxidative stress from the early development of Parkinson’s leads to impaired glucose metabolism.

Meanwhile, the results of a 2019 study indicate that increasing energy production levels can delay the onset of Parkinson’s symptoms.

An earlier study concluded that a drug used to treat prostate enlargement, called terazosin, could enhance cellular energy levels by increasing the activity of a key enzyme needed to break down glucose in glycolysis.

For this reason, the researchers from the 2019 study studied terazosin’s effects in animal models and used clinical databases to collect information about people with Parkinson’s disease who were taking the drug. They found that terazosin delayed the development of the disease, reduced complications, and reduced the number of diagnoses.

Now, an international team led by researchers from the University of Iowa has compared the effectiveness of glycolysis-enhancing drugs, including terazosin, with those of tamsulosin — a drug that has similar indications but does not increase glycolysis.

Their results were recently published in JAMA Neurology.

The researchers conducted two investigations, which involved collecting medical information from people who were new to taking terazosin, doxazosin, alfuzosin, or tamsulosin. All are glycolysis-enhancing except tamsulosin.

From January 1996 to December 2017, the team used data from three Danish nationwide health registries. From January 2001 to December 2017, they took information from the Truven Health Analytics Marketscan database.

The researchers excluded patients who had developed Parkinson’s disease before or within 1 year of taking the medication. They did not include any female participants because these drugs are typically prescribed to males.

Data collection began after the first year of starting the new medication. It continued until the person was removed from the database or until December 2017.

The researchers matched people taking glycolysis-enhancing drugs with people taking tamsulosin who had similar characteristics.

There were 52,365 matched pairs in the Danish cohort and 94,883 in the Truven cohort. The average age of the cohorts were 67.9 years and 63.8 years, respectively.

In both cohorts, people who took glycolysis-enhancing drugs were less likely to develop Parkinson’s disease than those who took tamsulosin.

People who took glycolysis-enhancing drugs had a 12% lower risk of developing Parkinson’s disease in the Danish cohort and a 37% lower risk in the Truven cohort, compared with people who took tamsulosin.

The researchers observed that for people who took a glycolysis-enhancing drug rather than tamsulosin, not only was there a reduction in the risk of developing Parkinson’s disease, but this risk continued to decrease the longer the person took the medication.

While the two investigations were “conceptually similar,” the team acknowledges that small design differences could have influenced the results.

“While the designs and outcome definitions used in the analyses were roughly parallel, differences between the two countries’ healthcare systems and coding practices make direct comparison between the Truven cohort and the Danish cohort difficult,” the authors write.

Many risk factors can contribute to the development of Parkinson’s disease, and the study did not look at other variables — such as head trauma or pesticide exposure — that could further increase disease progression.

Still, the authors suggest that identifying people with impaired glucose metabolism and prescribing glycolysis-enhancing drugs could help.

It is important to note that the study focused only on males, and it may be premature to suggest that females might benefit from this particular treatment.

A 2019 review in the Journal of Parkinson’s Disease reports that men are twice as likely to have Parkinson’s disease than women. However, in women, the disease is more likely to progress quickly, and women have higher mortality rates.

Because the present study was observational, further research, including randomized clinical trials, is needed to confirm that glycolysis-enhancing drugs can delay Parkinson’s disease in everyone.

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