Big data analytics has been applied to healthcare in different ways, including helping researchers validate basic ideas. A data-focused collaboration between scientists at Capital Medical University in Beijing and the University of Iowa found that a drug used to treat enlarged prostate could provide a new way to address Parkinson’s disease.
The drug is the decades-old terazosin, which is known as an alpha blocker because it reduces the effect of alpha-1 adrenergic receptors to induce the relaxation of smooth muscle in the prostate. Lei Liu, a professor at CMU’s Beijing Institute for Brain Disorders, and his team previously showed that the drug could activate an enzyme called PGK1, which is critical for the production of cellular energy, glycolysis.
That finding led Liu and UI’s Michael Welsh to the current Journal of Clinical Investigation study, which examined the drug’s potential use in Parkinson’s.
Researches have shown that Parkinson’s occurs when the cell’s energy factories, mitochondria, fail to function properly, leading to neuronal metabolism disruption and then nerve cell death. Several inherited forms of the disease are caused by mutations in cellular energy pathways, and people often develop Parkinson's as they grow old, when energy production naturally declines.
Could terazosin, by easing the energy shortage, help alleviate Parkinson's? The researchers tested the hypothesis in several models of the disease. They found that terazosin could prevent neurodegeneration when given before cell death, or slow or stop the decay after its onset.
“When we tested the drug in various different animal models of [Parkinson's], they all got better. Both the molecular changes in the brain associated with cell death and the motor coordination in the animals improved,” Liu said in a statement.
Many older men are already taking terazosin for enlarged prostate and could be at risk of developing Parkinson's. So Welsh turned to his colleagues at UI to see if existing patient databases could offer any clue as to whether terazosin has any correlation with the disease.
They first used the Michael J. Fox Foundation’s Parkinson's Progression Markers Initiative. Data showed that men on terazosin had reduced rates of progressive motor disability compared to those who were taking another prostate drug, tamsulosin, which does not target PGK1.
Problem was, the relatively small data bank only included 13 men on terazosin or two other PGK1 activating drugs. So to further confirm the findings, the team turned to the IBM Watson/Truven Health Analytics MarketScan Database, which includes records of more than 250 million people.
This time, the team identified 2,880 Parkinson's patients taking one of the three PGK1 drugs and 15,409 patients who were on tamsulosin. By studying these patients’ diagnoses and clinic visits, the team found that terazosin and its fellow PGK1 drugs reduced the signs, symptoms and complications of Parkinson’s, according to the statement.
Existing Parkinson's therapies mainly focus on increasing the levels of dopamine or dopamine-producing nerve cells in the brain. Researchers are looking at the possibility of reducing misfolded alpha-synuclein protein, which is believed to drive Parkinson’s by accumulating in the brain. The alpha-synuclein theory may also explain Parkinson's from the energy-supply perspective. A 2018 PNAS study found a buildup of the protein can impair the movement of mitochondria, resulting in the loss of synapses, which are the junctions between nerve fibers that allow them to communicate. German biotech Modag recently raised €12 million ($14 million) in series A to help fund in-human tests of its candidate, anle138b, an inhibitor of alpha-synuclein.
Based on their current findings, members of Liu and Welsh’s team are planning a phase 1/2 study of terazosin in Parkinson’s. Though the primary goal of the study is to assess the drug’s safety—not efficacy—the researchers hope “this study will guide future studies of [terazosin and similar] medications for the disease modification,” according to ClinicalTrial.gov. They also want to see if terazosin can help reverse energy shortages in Parkinson's.