Terazosin is an alpha blocker that reduces the effect of alpha-1 adrenergic receptors to induce the relaxation of smooth muscle in the prostate, which was previously shown to activate PGK1 enzymes important to the production of cellular energy glycolysis.
Parkinson’s disease has been shown to occur when mitochondria fail to function properly leading to neuronal metabolism disruption and nerve cell death. Some inherited forms of the disease are caused by mutation in cellular energy pathways, and sometimes the disease develops as people grow old when energy production declines.
As published in the Journal of Clinical Investigation to test if terazosin could help alleviate the disease by easing the energy shortage the hypothesis was tested in several models of Parkinson’s disease, in which it was shown to prevent neurodegeneration when given before cell death, and slow or stop decay after 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,” said Lei Liu, a professor at CMU’s Beijing Institute for Brain Disorders in a statement.
Existing patient databases were examined to investigate whether terazosin has any correlation with Parkinson’s disease by first using the Michael J. Fox Foundation’s Parkinson’s Progression Markers Initiative; analysis showed those taking the drug had decreased rates of progressive motor disability compared to those taking tamsulosin which doesn’t target PGK1.
Next the team looked at the IMB Watson/Truven Health Analytics MarketScan Database which included over 250 million people to confirm their findings: 2,880 patients with Parkinson’s disease were identified taking one of the 3 PGK1 drugs and 15,409 who were taking tamsulosin; analysis showed that terazosin and fellow PGK1 drugs reduced the signs, symptoms and complications of Parkinson’s disease.
Based on their findings a phase 1/2 study of the effects of terazosin on Parkinson’s disease is being planned, with the primary goal to assess the safety of the drug not its efficacy, as well as to see if the drug can help to reverse energy shortages in the disease, which is hoped to help guide future studies of medications for modification of Parkinson’s disease.
