Click the play button for the audio version of this Research Summary
Capitalising on the neuroprotective effects of a prostate drug
Original article: Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases. J Clin Invest: September 16, 2019
A drug used often to manage an enlarged prostate has been shown in a series of animal models to exert neuroprotective effects, and may be associated with a reduction in Parkinson’s risk.
Why is it important?
It highlights the diverse effects of commonly prescribed medications, and the importance of energy balance in neurons in the context of neuroprotective strategies.
- Novelty 90% 90%
- Proximity 70% 70%
- Deliverability 70% 70%
This is an exciting result as it highlights yet another clinically available drug that could potentially be repurposed for Parkinson’s. Not only does this report provide preclinical evidence in models of Parkinson’s, but also epidemiological data suggesting that this drug could be useful for Parkinson’s. A clinical trial of Terazosin in Parkinson’s has been initiated, but caution will need to be taken as this drug lowers blood pressure, and people with Parkinson’s can already have low blood pressure levels.
It is estimated that by age 90, approximately 60% of all men are affected by benign prostatic hyperplasia, an age-related enlargement of the prostate condition which causes problems with urination in men. One of the drugs used to manage the troublesome and potentially serious consequences of an enlarged prostate gland is terazosin, which helps to relax involuntary muscle around the body which is also found around blood vessels. For this reason, it is known as a “relaxer” and is also used to reduce high blood pressure.
However, experiments have shown that in addition to these effects, terazosin also stimulates a substance found inside all cells in the body known as PGK1, which is a rate limiting step for the breakdown of glucose into energy.
A group of collaborating researchers from China and the US investigated whether daily terazosin injections would slow down or reduce neurodegeneration in mice caused by two different toxins used routinely in the lab to create animal models of Parkinson’s. Indeed, after injecting the toxins and following up with a week of treatment with terazosin, the scientists found that more neurons had survived and that the animals’ performance was also less impaired compared to those that did not receive the drug. In a separate group of transgenic mice which overproduce alpha synuclein (the protein which misfolds into harmful clumps that damages neurons in Parkinson’s), they addressed the effects of 12 months of treatment with terazosin. They saw that terazosin mitigated both alpha synuclein build up as well as the movement related problems seen in these animals.
Since terazosin has been in use now for several decades, the researchers then turned to a large medical database (the IBM Watson/Truven database), which holds pharmaceutical claims and diagnoses for several thousand individuals. They identified 2880 people with Parkinson’s who were also taking terazosin, or other similar drugs for prostate enlargement. They found that claims for terazosin (or similar drugs) were associated with a 20% lower risk of having any of the 79 Parkinson’s-related diagnostic codes.
If terazosin is to be trialed in people with Parkinson’s, small scale phase II studies in people with Parkinson’s must first establish whether it is safe and well tolerated alongside commonly used medications such as levodopa.
Original article: Cai R, Zhang Y, Simmering JE, Schultz JL, .., Liu L. September 16, 2019. Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases.