Terazosin for Parkinson's Disease (TZ-PD) Trial

[Bolt_Upright]

Terazosin

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Somebody in a different forum posted that the best medicine they are taking for PD is Terazosin off label. He said his movement specialist said he was better now than he was 7 years ago.

I see Terazosin has been posted about before here, but did not get much attention.

There are 2 trials going on:

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Terazosin for Parkinson's Disease (TZ-PD) Trial

Drug: Terazosin 5 MG

clinicaltrials.gov/ct2/show...

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Terazosin Effect on Cardiac Changes in Early Parkinson's Disease Trial Recruiting

clinicaltrials.gov/ct2/show...

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And a sprinkling of stories:

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Could a prostate drug slow or stop Parkinson’s?

medium.com/parkinsons-uk/co...

Further evidence emerges to suggest that terazosin — a drug currently used to treat enlarged prostate — may have the potential to slow or stop Parkinson’s.

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Recent developments in the treatment of Parkinson's Disease 2020

ncbi.nlm.nih.gov/pmc/articl...

Terazosin, an α 1-adrenergic antagonist used in benign prostatic hypertrophy, has recently emerged as a putative treatment for PD. Terazosin has been found to activate phosphoglycerate kinase-1 and the chaperone protein HSP90, which is involved in multiple intracellular stress responses 46. It has been shown to have neuroprotective effects in neurotoxin models of nigrostriatal degeneration in invertebrates and rodents, including after delayed administration 35. Additionally, terazosin reduced α-synuclein levels in transgenic mice and in neurons derived from patients with LRRK2 mutation-associated PD 35. Furthermore, a retrospective epidemiological study found that people taking terazosin have a reduced relative risk of PD 35. These promising findings have led to terazosin rapidly progressing to a randomised placebo-controlled trial, which will involve 20 patients with Hoehn and Yahr stage 3 PD (NCT03905811). However, terazosin reduces blood pressure and can cause orthostatic hypotension, which is a problem in many patients with advancing PD and may limit its applicability in this disease.

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Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases 2019

jci.org/articles/view/129987

Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs.

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Blood Pressure and Prostate Treatment May Prevent or Slow Parkinson’s, Early Study Suggests - 2019

parkinsonsnewstoday.com/201...

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.

Sounds very interesting to me.

I know one person on this forum's PwP's ankles swelled up, so it is not perfect. Interesting though.

[Hidden]

Causes constipation

[Hidden]

did anyone try it here?

[humph3 in reply to Hidden]

As I have enlarged prostate and NMD I asked to be put on to terazosin. I have been taking it for 1 year and as it works better for my prostrate am happy to carry on. I don’t think my movement disorder has got any worse

[Ibjcarp in reply to humph3]

Do you take 6mg per day?

[humph3 in reply to Ibjcarp]

I take 2mg per day is 6 the recommended dose for treating neurological conditions?

[Hidden]

JerryinSATX pwpwifekim any updates?

[JerryinSATX in reply to Hidden]

Terazosin has helped my prostate issues and my PD symptoms have stabilized generally.

[pwpwifekim in reply to Hidden]

Sorry for the delay, Nedim. No updates, nor do I expect any. All’s well.

[Hidden]

It is interesting given its potential impact on alpha synuclein aggregation, this article puts it in the hunt with Nilotinib, Exenatide and even cites Ambroxol.

"The authors speculate that the putative increase in ATPassociated with TZ may push the equilibrium of aggregated vs soluble alpha synuclein in a beneficial directionor may have an anti-apoptotic effect. If so, then this intervention may have relevance for the broaderpopulation of PD patientsrather than just the “mitochondrial” subgroup of patients. In summary, TZ has certainly suddenly leapt into a growing pool of drugs that have a repurposed role in PD, such as Exenatide, Salbutamol, UDCA, Nilotinib, Deferiprone and Ambroxol."

discovery.ucl.ac.uk/id/epri...

As you say however, there are some side effects that are a little more concerning to me than other options. We should keep a watch out on its trials.

rxlist.com/hytrin-side-effe...

[Bolt_Upright in reply to Hidden]

Thanks DHPSR. Those are some serious side effects, but still looks like you'd have maybe a 60 or 70% chance of no side effects (just my guess). Thanks for the link.

[WinnieThePoo]

It's looked at for it's potential to slow progress so I wouldn't expect reported symptom relief. Indeed chances are that would be a placebo effect. Disease progress is hard to assess individually, but my neurologist recently was astonished at the slow progression of my disease. I started doxazosin 4mg a couple of years ago.

[Bolt_Upright in reply to WinnieThePoo]

And the list keeps growing! Thanks! Doxazosin. Looks like a similar drug.

[WinnieThePoo in reply to Bolt_Upright]

It's another alpha blocker /pgk1 inhibitor and was in the other group from Flomax with terazosin, in the study which highlighted the slower progression /milder symptoms

[Zella23]

My husband takes terrazozin for prostate issues, changed to it over a year and a half ago. Not changed PD meds since then so Neuro very impressed at his review in May. Had PD for 9 years dx for 5. He does take supplements and uses red light hat as well. Hopefully it is a combo of everything but who knows with this condition.

[WinnieThePoo in reply to Zella23]

Yes - I use the red light hat too - although fairly recently. I was also on the SPARK trial which just because they stopped it, doesn't mean it had no effect. So a combination of things, but I am encouraged to continue with Doxazosin - especially since I have experienced no adverse side effects with it (I have fairly high blood pressure - controlled by 20mg Lercadipine daily). My neurologist couldn't believe I was 4 years post-diagnosis. Partly, as I pointed out to her, this was due to only actually being 3 1/2 years post-diagnosis

[Zella23 in reply to WinnieThePoo]

It could be the Spark trial helped with slowing your progress, as you say it could be a combination of things. Yes my husband changed blood pressure pills due to GP worried Terrazozin would alter his BP. Only takes Indapamide now as Terrazozin regulates BP as well. He began on BP meds just about 8 months before dx with PD - he had issues with side effects and changed meds before finding one with fewer side effects. We ll never know if this contributed to PD - not sure we ll ever know!

[pwpwifekim]

HWP had been taking medication to control blood pressure for many years. In 2019 we convinced his GP (with MDS approval) to switch his medication to 5mg Terazosin. He has had no adverse side effects. While his Parkinson’s symptoms did not reverse, it may be slowing the progression. We will likely never know as he began taking c/l within a few months. Conclusion for this small trial is no harm, benefits not known. We do not plan to make any changes, but continue it.