Terazosin, a drug currently prescribed for patients with high blood pressure or enlarged prostates, may hold therapeutic potential to slow the progression of motor neuron diseases (MNDs) such as amyotrophic lateral sclerosis (ALS), according to new research findings.
MNDs are hard-to-treat, rare neurological diseases that destroy motor neurons and cause patients to slowly lose muscle function. Motor neurons have to create energy to transmit instructions from the brain to the muscles. Without enough energy, messages aren’t sent effectively, and movement is impacted.
While it’s still unclear why motor neurons die among MND patients, researchers do know that the neurons’ energy production drops early in disease progression. Terazosin—an antihypertensive drug and urinary retention med sold under Abbott’s brand name Hytrin, among others—has been shown to boost energy production in stroke and Parkinson’s disease models.
So scientists from the University of Edinburgh and the University of Oxford in the U.K. assessed terazosin’s effect on motor neurons using zebrafish, mice and stem cell models. The researchers discovered that the drug was tied to an increase in energy production that protected against the death of motor neurons, according to findings published Aug. 10 in eBioMedicine.
The team focused on PGK1, an enzyme involved in energy production. An MND mouse model showed terazosin protected motor neurons, offsetting the progression of paralysis and improving survival. In a stem cell model, the researchers found that motor neurons grown in a dish were protected by terazosin via increased energy levels. Additionally, zebrafish MND models demonstrated that either genetically increasing PGK1 amount or administering terazosin to elevate PGK1 activity improved motor neuron growth.
“We urgently need to accelerate the way drugs are developed from laboratory models into trials in patients,” Kevin Talbot, professor at the University of Oxford and study co-lead, said in a related news release. “Our work uses a combination of approaches to increase the confidence that drugs will actually work in people with MND and significantly slow disease progression. It represents an important new step in the search for therapies.”
The team has now launched a study that will examine how terazosin works on key indicators of disease progression in 50 MND patients.
“The benefit of working with terazosin is that it is already prescribed for a different health condition, so we know that it is safe for humans and could quickly move to the clinic,” said Helena Chaytow, Ph.D., of the University of Edinburgh and first author of the study.
If the 50-patient study is successful, the researchers aim to start a full clinical trial.