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Large data analysis has been applied to health care in a variety of ways, including helping researchers validate basic ideas. Data-driven collaboration between scientists at Capital Medical University in Beijing and the University of Iowa revealed that a drug used to treat prostate enlargement could be a new way to fight the disease. Parkinson.
The drug is 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 prostate smooth muscle. Lei Liu, a professor at the CMU Institute of Brain Disease in Beijing, and his team have already shown that the drug can activate an enzyme called PGK1, essential for the production of cellular energy, glycolysis.
This discovery led Liu and Michael Welsh of UI to the ongoing study of the Journal of Clinical Investigation, which focused on the potential use of the drug in the treatment of Parkinson's disease.
Studies have shown that Parkinson's disease occurs when the cell's energy plants, the mitochondria, do not function properly, resulting in disruption of neuronal metabolism, followed by death of nerve cells. Several inherited forms of the disease are caused by mutations in cellular energy pathways, and people often develop Parkinson's disease as they age, when energy production naturally decreases.
Could terazosin, by alleviating the energy shortage, help relieve Parkinson's disease? The researchers tested the hypothesis in several models of the disease. They discovered that terazosin could prevent neurodegeneration when it was administered before cell death, or slow down or stop degradation after it has occurred.
"When we tested the drug on different animal models of [Parkinson’s]they all improved. The molecular changes in the brain associated with cell death and motor coordination in animals have improved, "Liu said in a statement.
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Many older men are already taking terazosin for an enlarged prostate and are at risk of developing Parkinson's disease. Welsh therefore turned to his colleagues in the user interface to see if existing patient databases could offer a clue as to the eventual correlation between terazosin and the disease.
They first used the Parkinson's Progress Markers initiative of the Michael J. Fox Foundation. Data showed that men taking terazosin had lower rates of progressive motor disability than men taking another anti-prostate drug, tamsulosin, which does not target PGK1.
The problem was that the relatively small database consisted of only 13 men treated with terazosin or two other drugs that activated PGK1. In order to further confirm the findings, the team turned to the MarketScan database of IBM Watson / Truven Health Analytics, which contains records of over 250 million people.
This time, the team identified 2,880 patients with Parkinson's disease taking one of three PGK1 medications and 15,409 patients treated with tamsulosin. By studying the diagnoses of these patients and visiting the clinic, the team found that terazosin and its other medications, PGK1, reduced the signs, symptoms, and complications of Parkinson's, the statement said.
RELATED: Modag raises series A round to test the drug Parkinson's disease-modifying disorders
Existing Parkinson's therapies focus primarily on increasing levels of dopamine or dopamine-producing nerve cells in the brain. Researchers are studying the possibility of reducing misfolded alpha-synuclein protein, which could lead to Parkinson's disease by accumulating in the brain. The theory of alpha-synuclein can also explain Parkinson's disease from the point of view of energy supply. A 2018 PNAS study found that an accumulation of protein could hinder the movement of mitochondria, resulting in the loss of synapses, junctions between nerve fibers that allowed them to communicate. The German biotech Modag recently raised 12 million euros ($ 14 million) from the A series in order to fund the inhumane tests of its candidate, anle138b, an alpha-synuclein inhibitor.
Liu and Welsh's team are currently planning a phase-one study of terazosin for the treatment of Parkinson's disease. Although the primary goal of the study is to evaluate the safety of the drug – not its efficacy – the researchers hope that "this study will guide future studies of [terazosin and similar] drugs for disease modification, "according to ClinicalTrial.gov They also want to see if terazosin can help address energy shortages in Parkinson's disease.
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