A new study provides more "compelling" evidence that glycolysis-enhancing alpha-1-blockers used to treat benign prostatic hypertrophy (BPH) may be neuroprotective. In a large observational study, use of terazosin (TZ), doxazosin (DZ) or alfuzosin (AZ) was associated with a decreased risk of Parkinson's disease (PD) compared with use of tamsulosin, an alpha-1-blocker also prescribed for BPH that does not enhance glycolysis. Glycolysis and mitochondria function are decreased in people with PD, Dr. Jacob Simmering of the University of Iowa, in Iowa City, and colleagues explain in JAMA Neurology. TZ/DZ/AZ, but not tamsulosin, have been shown to enhance glycolysis, providing a unique opportunity to use tamsulosin as a control to test the potential neuroprotective effects of the other three drugs. Using Danish nationwide health registries and the Truven Health Analytics MarketScan, the researchers created more than 147,000 propensity-score-matched pairs of men initiating TZ/DZ/AZ or tamsulosin for BPH or unspecified urinary problems, with at least one year of follow-up. They found that use of glycolysis-enhancing TZ/DZ/AZ was associated with significant decreases of 12% to 37% in PD risk compared with use of tamsulosin. "We have previously shown that terazosin and similar medications modify disease severity in animal models (flies and rodents) of Parkinson's disease," Dr. Simmering told Reuters Health by email. "We have also previously seen less frequent visits for Parkinson's disease symptoms in patients with Parkinson's disease among users of these drugs. However, it was unknown if terazosin and similar medications affected the risk of developing Parkinson's disease in the first place," he said. "The combination of the strength of these results from two large databases in two different countries with different cultural and health care systems, the prior mechanistic studies, the results in animal models of PD, and the prior observational results from patients with PD provide compelling evidence that glycolysis-enhancing drugs might be neuroprotective and prevent or delay the development of PD.," the researchers conclude in their paper. They note that the pathophysiology of PD is heterogeneous and research is needed to identify whether certain people are more likely to benefit from glycolysis-enhancing drugs. "While our results - especially the consistency between the American and Danish cohorts and the consistency with previous lab work - are suggestive of a protective effect with terazosin, a randomized controlled trial is required before we can make any inference to clinical practice," Dr. Simmering told Reuters Health. "If these results are supported by a clinical trial, terazosin and other glycolysis-enhancing medications could potentially offer a neuroprotective treatment for people with newly diagnosed Parkinson's disease," he said. The study had no commercial funding and the authors have no conflicts of interest. —Megan Brooks Source
