Could prostate drugs minimize the risk of Parkinson’s disease?

A new study suggests that repurposing glycolysis-enhancing drugs such as terazosin, usually used for the treatment of an enlarged prostate, could decrease the risk of male Parkinson’s disease.

A neurodegenerative condition caused by decreased levels of a brain chemical called dopamine is Parkinson’s disease. The symptoms worsen over time, and from having trouble speaking to difficulty chewing and swallowing, the disease may have a wide variety of complications.

While Parkinson’s disease mostly affects movement, loss of dopamine may also trigger non-motor symptoms, including depression, dementia, sleep issues, and low energy levels.

The wide spectrum of symptoms can be addressed by different medications, but currently, no drug can cure Parkinson’s disease.

Most therapies focus on the restoration of levels of dopamine. More research has recently, however, investigated ways of increasing energy levels using a metabolic pathway called glycolysis.

The role of glycolysis in Parkinson’s

To carry out their roles, all cells need energy, and glycolysis is one of the first metabolic pathways in the production of energy.

This multi-stage pathway breaks down glucose into various types of molecules that are used for the further processing of energy.

The results of a 2014 study indicate that elevated oxidative stress contributes to impaired glucose metabolism from the early development of Parkinson’s.

The findings of a 2019 report, meanwhile, suggest that increasing levels of energy production can delay the onset of symptoms of Parkinson’s.

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

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

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

Recently, their findings were published in JAMA Neurology.

Investigations in the US and Denmark

The researchers performed two experiments involving the collection of medical information from people new to the use of terazosin, doxazosin, alfuzosin, or tamsulosin. All are glycolysis-enhancing except tamsulosin.

The team used data from three Danish country-wide health registries from January 1996 to December 2017. They took details from the Truven Health Analytics Marketscan database from January 2001 to December 2017.

Before or within 1 year of taking the drug, the researchers removed patients who had acquired Parkinson’s disease. They did not have any female participants since these medications are usually administered to males.

After the first year of beginning the new drug, data collecting began. It continued until the person was taken out of the database or until December 2017.

Which drugs reduced Parkinson’s risk?

The researchers compared individuals who took glycolysis-enhancing drugs with individuals who had similar characteristics who took tamsulosin.

There were 52,365 paired pairs in the cohort of Denmark and 94,883 in the cohort of Truven. The cohorts’ average age was 67.9 years and 63.8 years, respectively.

People who took glycolysis-enhancing medications were less likely than those who took tamsulosin to develop Parkinson’s disease in both cohorts.

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

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

Although the two study experiments were “conceptually similar,” the team admits that the outcomes may have been affected by minor design variations.

“While the designs and outcome definitions used in the analyses were roughly parallel, differences between the health care systems and coding practices of the two countries make it difficult to directly compare the Truven cohort with the Danish cohort,” the authors write.

Some considerations about the drugs

Many risk factors may lead to the development of Parkinson’s disease, and the research did not look at other variables that may further increase disease progression, such as head trauma or pesticide exposure.

Nevertheless, the authors say that it could help to recognise people with impaired glucose metabolism and prescribe glycolysis-enhancing drugs.

It is important to note that the research focused on males only, and it may be premature to conclude that this particular treatment may benefit females.

In the Journal of Parkinson’s Disease, a 2019 study states that men are twice as likely than women to have Parkinson’s disease. However, the disease is more likely to advance rapidly in women, and women have higher mortality rates.

Further testing, including randomized clinical trials, is required to confirm that glycolysis-enhancing drugs will delay Parkinson’s disease in anyone, since the current study was observational.

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