JAMA Neurol: The relationship between α-1 blockers and the risk of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease.
prevention or delay in PD development is a key clinically unsealed need.
recently found in animal models and human clinical databases that tracodone and drugs closely related to it can enhance glycolysis, thereby reducing the progression of Parkinson's disease.
In order to determine whether tracosin, dosazine, and aphdone were associated with a reduced risk of Parkinson's disease, researchers tested this hypothesis using data from two large administrative health care databases in the United States and Denmark.
findings were published recently in the journal JAMA Neurology.
The cohort study used active control and tendency score matching data from the Danish National Health Registry, including the Danish National Prescription Registry, the Danish National Patient Registry and the Danish Civil Registration System, as well as data from the Truven Health Analytics MarketScan database from January 1996 to December 2017 and from January 2001 to December 2017.
, the database includes all residents, while the Truven database is a compilation of insurance claims across the United States.
data from February 2019 to July 2020.
the researchers also performed additional dose response analyses in patients who used trasazole/dosazazine/aphdoxin vs tansorosin.
outcomes and measurements: differences in PD incidence risk identified by diagnosis or use of PD-specific drugs among patients who have used trasazole/dosazine/aphdoxin or tansorosin.
results showed that 52,365 pairs of terazine/dosazine/afasin users, all male, with an average (SD) age of 67, were identified in the Danish Registry. .9 (10.4) years; 94,883 pairs of tendentive scores were identified in the Truven database, all of which were male, with an average (SD) age of 63.8 years (11.1) years.
the risk ratio (HR) for PD was 0.88 (95%CI, 0.81-0.98) for patients using tradium/dosazazine/afaazine in the Danish queue, and 0.63 (95% CI, 0.58-0.69) for patients in the Truven queue.
in the Danish and Truven queues, HR reductions in short-, medium- and long-term users of trasazole/dosazazine/afaazine were associated with dose reactions.
results of the cumulative incidence of Parkinson's disease (PD) in the Danish and Truven queues showed that men taking TZ/DZ/AZ (Trasazole/dosazine/afasin) had a 12 to 37 percent lower risk of PD than men taking Tansorosin.
TZ/DZ/AZ for a long time was associated with a greater reduction in observed hazards than the use of tansorosin over the same period of time.
and TZ/DZ/AZ was associated with slow progression and reduced complications in patients with PD.
molecular mechanisms of these effects, such as TZ/DZ/AZ, have been confirmed by earlier studies.
TZ/DZ/AZ enhances PGK1 activity, thereby increasing glycolysis and cell ATP levels.
these changes may prevent PD neurodegenerative changes in at least two ways.
, PD exhibits deficiencies in energy metabolism, such as attation-related ATP and decreased energy metabolism, genetic defects in mitochondrial function, and toxin suppression of mitochondrial function.
TZ/DZ/AZ can offset these defects by enhancing glycolysis and increasing ATP levels.
second, assume that α-synuclein's aggregate induces neurodegenerative changes in PD.
TZ/DZ/AZ elevates ATP, which is a hydrolyzed enzyme that may prevent aggregates from forming and dissolving previously formed aggregates.
therefore, if the assumed relationship between α-synuclein and neurodegenerative degeneration is correct, TZ/DZ/AZ may reduce the risk of PD's risk of aggregation neurodegenerative change by preventing PD.
, however, the assessment of this hypothetical mechanism is beyond the scope of this study.
combination of these and other mechanisms is also possible, including ATP-dependent decommeration and reducing apoptosis in mates.
further research is needed to determine whether a specific subset of patients is more likely to benefit from treatment.
these considerations, future work, especially in the form of randomized trials, needs to adequately address the causality of TZ/DZ/AZ.
: Simmering JE, Welsh MJ, Liu L, Narayanan NS, Pottegård A. Association of Glycolysis-Enhancing α-1 Blockers With Risk of Developing Parkinson Disease. JAMA Neurol. Published online February 01, 2021. doi:10.1001/jamaneurol.2020.5157MedSci Original Source: MedSci Original Copyright Notice: All notes on this website "Source: Met Medical" or "Source: MedSci Original" text, images and audio and video materials, copyrights are owned by Metz Medicine, without authorization, no media, website or individual may reproduce, authorized to reproduce with the words "Source: Mets Medicine".
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