Terazosin and PGK1 glycolysis

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Rong Cai, Lei Liu, Nandakumar Narayanan, Michael Welsh and colleagues (Iowa). J Clin Invest 2019;129:4539–4549. Cohort studies: Simmering, Welsh, Liu, Narayanan and Pottegård (JAMA Neurol 2021;78:407–413, Danish registries and a US claims database), and Sasane et al. (J Clin Invest 2021;131:e145112, a US database study funded by Cerevel Therapeutics, a company developing Parkinson's drugs).

What happened

Cells low on energy (landmark 11) might be helped by running glycolysis (sugar breakdown) harder. The 2019 paper, "Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases", reported that terazosin raised brain ATP and slowed or prevented neuron loss in toxin and genetic models (mice, rats, flies and patient stem-cell neurons), and that people taking terazosin and related drugs in two human databases had slower progression and fewer diagnoses.

• For. Simmering 2021: among men, terazosin, doxazosin or alfuzosin users had a hazard ratio of 0.88 (95% CI 0.81–0.98) in Denmark (52,365 matched pairs) and 0.63 (0.58–0.69) in the US claims database (94,883 pairs) against tamsulosin users, with lower hazard for longer use.
• Against. Sasane 2021 (113,450 people): Parkinson's incidence was 1.53% in tamsulosin users, 1.10% in terazosin/alfuzosin/doxazosin users and 1.01% in matched controls. Zosin users did not differ from controls (P = 0.29), so tamsulosin may raise risk rather than terazosin lower it.

Why it moved us toward a cure

It is a cheap, approved drug aimed at neuronal energy. Terazosin is one of the two drug arms (with telmisartan) of the UK platform trial, landmark 80; its registry record NCT07207057 shows recruiting since September 2025. A 13-person Iowa pilot (NCT03905811, completed) and an extension study (NCT05109364) are registered; a 2025 dose-finding study in 18 healthy older adults (Schultz et al., J Parkinsons Dis 15:1253) found 5 mg/day raised blood ATP and lowered brain FDG uptake, with no extra effect at 10 mg.

Outcome

Open. Observational data conflict; the randomised answer is awaited (the platform trial's primary completion is estimated for 2031). I found no correction or retraction of the key papers.

Sources

• Cai et al., J Clin Invest 2019, DOI 10.1172/JCI129987 · Sasane et al., J Clin Invest 2021, DOI 10.1172/JCI145112
• Simmering et al., JAMA Neurol 2021, DOI 10.1001/jamaneurol.2020.5157
• ClinicalTrials.gov NCT07207057 · NCT03905811
• Schultz et al., J Parkinsons Dis 2025, DOI 10.1177/1877718X251356503
• Not yet verified: the results of the Iowa pilot (posted on the registry, not read); the platform-trial dose; funders of Cai 2019.