Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson’s, Early Study Suggests

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Source: parkinsonsnewstoday.com

People taking Hytrin (terazosin) or similar medications to treat high blood pressure and benign prostatic hyperplasia may be less likely to develop Parkinson’s disease, an early study suggests.

Parkinson’s patients who use these medications may also see their disease progress more slowly and with fewer complications, its researchers report.

The study, “Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases,” was published in the Journal of Clinical Investigation.

Hytrin is indicated for the treatment of non-cancerous prostate enlargement and high blood pressure (hypertension). The medication, available as a generic (terazosin), acts on the alpha-1 adrenergic receptor to block adrenaline’s action, relaxing smooth muscle in both the blood vessels and the prostate, allowing blood and urine, respectively, to flow more easily.

Experts agree that energy metabolism plays a central role in the molecular mechanism of neurodegenerative diseases like Parkinson’s. In fact, problems in energy metabolism and low levels of cellular energy are common features of this disorder.

Hytrin has been shown to enhance the activity of a protein called phosphoglycerate kinase 1 (PGK1), which is involved in a critical energy-producing process known as glycolysis, where the simple sugar glucose is broken down by cells to produce energy. Boosting PGK1 activity increases the number of energy molecules, also known as ATP, within a cell.

Because low levels of ATP have been observed in Parkinson’s, increasing the breakdown of glucose and hence cellular energy, in theory, may slow down or prevent the neurodegenerative processes underlying this disease.

Researchers at Capital Medical University in Beijing, decided to test this hypothesis and investigate whether increasing PGK1 activity levels would change the course of Parkinson’s disease.

Hytrin was found to increase brain ATP levels and slow or prevent nerve cell loss in several models of Parkinson’s (MPTP, rotenone and 6-OHDA-induced or genetic models): mice, rats, flies, and induced pluripotent stem cells. MPTP, rotenone and 6-OHDA are all neurotoxins that induce death of dopamine-producing neurons and mimic Parkinson’s symptoms.

Treatment with this medication increased brain dopamine levels — the chemical messenger that is present in low levels in the brains of Parkinson’s patients — and partially restored motor function in both mice and flies.

Importantly, boosting PGK1 activity was beneficial even when treatment was initiated after the onset of neurodegeneration, suggesting the modulation of this protein’s function could help to slow Parkinson’s progression.

Because Hytrin is prescribed for other diseases, scientists also studied two human databases — the Parkinson’s Progression Markers Initiative and the IBM Watson/Truven database — looking for a possible Hytrin effect in relation to Parkinson’s disease.

These two data sets  included a total of 4,072 individuals on Hytrin, doxazosin, or alfuzosin. The latter two medications produce effects similar to those of Hytrin.

A retrospective analysis on both databases revealed that use of Hytrin and related agents slowed Parkinson’s disease progression, reduced the number of neurodegeneration-related complications, and lessened the risk of a Parkinson’s diagnosis, compared to people not using these medications.

“These findings identify a protein and a pathway that might be targeted to slow or prevent neurodegeneration in PD [Parkinson’s disease] and potentially other neurodegenerative diseases with altered energy balance,” the researchers concluded.

Terazosin, available only by prescription, can cause dizziness and fainting because it lowers blood pressure.