A drug to treat high blood pressure could also be used against conditions such as Parkinson’s, Huntington’s and forms of dementia a new study suggests.
University of Cambridge researchers have shown that felodipine, a hypertension drug, may be a candidate for re-purposing after showing promise when treating neurodegenerative diseases. A common feature of these diseases is the build-up of misfolded proteins. These proteins, such as huntingtin in Huntington’s disease and tau in some dementias, form “aggregates” that can cause irreversible damage to nerve cells in the brain.
In healthy individuals, the body uses a mechanism known as autophagy, or “self-eating”, to prevent the build-up of such toxic materials. This involves “Pac-Man”-like cells eating and breaking down the materials. However, in neurodegenerative diseases this mechanism is impaired and unable to clear the proteins building up in the brain.
As there are currently no drugs that can induce autophagy effectively in patients, and an increasing number of people are being diagnosed with neurodegenerative diseases as we live longer, scientists have begun looking to re-purpose existing drugs in addition to searching for new drugs.
In a study published in Nature Communications, scientists at the UK Dementia Research Institute and the Cambridge Institute for Medical Research at the University of Cambridge have shown in mice that felodipine may be a candidate for re-purposing.
Previous studies have already hinted at a possible link between the drug and reduced risk of Parkinson’s disease, but now the researchers have shown that it may be able to induce autophagy in several neurodegenerative conditions. Mice that had been genetically modified to express mutations that cause Huntington’s disease or a form of Parkinson’s disease, and zebrafish that model a form of dementia, were used in the study.
Felodipine was effective at reducing the build-up of aggregates in the mice with the Huntington’s and Parkinson’s disease mutations and in the zebrafish dementia model. The treated animals also showed fewer signs of the diseases.
Mice are a useful model for studying human disease as their short life span and fast reproductive rate make it possible to investigate biological processes in many areas. Their biology and physiology have a number of important characteristics in common with those of humans, including similar nervous systems.
Professor David Rubinsztein, who led the study, said: “This is the first time that we’re aware of that a study has shown that an approved drug can slow the build-up of harmful proteins in the brains of mice using doses aiming to mimic the concentrations of the drug seen in humans,” says Professor Rubinsztein. “As a result, the drug was able to slow down progression of these potentially devastating conditions and so we believe it should be trialled in patients.”
“This is only the first stage, though. The drug will need to be tested in patients to see if it has the same effects in humans as it does in mice. We need to be cautious, but I would like to say we can be cautiously optimistic.”
Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: “The promising results show the drug worked in mice at levels that are well-tolerated in humans and researchers will now need to be test the drug in people with diseases that cause dementia. We haven’t seen a new dementia drug in over 15 years and it’s important that scientists explore all potential avenues to deliver a treatment that will change lives.”