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A blood pressure drug taken by thousands of Britons could combat Alzheimer’s disease, according to new research.
Human trials of felodipine, which has been prescribed for the last three decades, are already being planned.
Experiments in mice found it destroys rogue chemicals in the brain called tau.
They collect in tangles, killing neurons and causing memory loss and confusion.
These misfolded proteins have also been linked to Parkinson’s disease as well as Huntington’s disease – which triggers similarly devastating symptoms to dementia.
Study leader Professor Dr David Rubinsztein said: “This is the first time we are aware of a study has shown 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.
“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.”
The findings published in Nature Communications were also replicated in the brains of zebrafish that have similar chemical pathways to a human’s.
The professor of molecular neurogenetics at the University of Cambridge and UK Dementia Research Institute, added: “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.”
He added: “We need to be cautious, but I would like to say we can be cautiously optimistic.”
The build up of misfolded proteins is a common feature of all three conditions, collectively known as neurodegenerative diseases.
These molecules such as in Huntington’s and tau in some forms of dementia, including Alzheimer’s, form ‘aggregates’ that can lead to irreversible nerve cell loss in the brain.
In healthy individuals, the body uses a mechanism to stop these toxic materials from gathering.
Known as autophagy, it involves ‘Pac-Man’-like cells eating and breaking down the materials.
In neurodegenerative diseases this mechanism is impaired and unable to clear the proteins building up in the brain.
In 2016, Japanese scientist Yoshinori Ohsumi won the Nobel Prize for his research on the autophagy.
These have led to a better understanding of diseases such as Parkinson’s and dementia.
Since then, drug companies and academics have raced to find drugs that will stimulate the process.
As the global population ages, an increasing number of people are being diagnosed with brain illnesses, making the search for effective drugs ever more urgent.
Currently none can induce autophagy effectively in patients.
So scientists are increasingly looking to re-purpose existing medications. These have the advantage they have already been shown to be safe for use in humans.
If they can be shown to be effective against the target diseases, then the journey to clinical use is much faster.
Tests on the lab rodents showed felodipine may be a candidate for Alzheimer’s, Parkinson’s and Huntington’s.
Known as a calcium channel blocker, lowers blood pressure by relaxing the muscles of the heart and vessels.
Epidemiological studies have already hinted at a possible link between the drug and reduced risk of Parkinson’s.
But now the researchers have demonstrated it may be able to induce autophagy in several neurodegenerative conditions.
Dr Rubinsztein and colleagues used mice that had been genetically modified to express mutations that cause Huntington’s or a form of Parkinson’s, and zebrafish that model a form of dementia.
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.
Felodipine reduced the number of damaging proteins in the mice with Huntington’s and Parkinson’s – and in the zebrafish with the dementia type condition.
The treated animals also showed fewer signs of the diseases.
Studies in mice often use doses that are much higher than those known to be safe to use in humans.
The Parkinson’s mice showed beneficial effects even at concentrations similar to those tolerated by humans.
The researchers did this by controlling the amounts of the drug using a small pump under the mouse’s skin.
Dr Rubinsztein said: “Our data suggest felodipine induces autophagy in neurons and enhances removal of a range of disease-causing proteins.
“Importantly our zebrafish data suggest that the rescue of tau toxicity is autophagy-dependent.
“A major attraction of drug repurposing is that this strategy offers the possibility of rapid transitioning from preclinical models to patients, as the toxicity and tolerability profiles of the relevant compounds are known.”
He added: ” These data support testing in humans with appropriate neurodegenerative diseases.
“Indeed, when a drug is safe and well tolerated, the possibility of preventive treatments aiming to delay disease onset also becomes an option.”
In the UK there are about 850,000 people living with dementia, a figure set to rise to 2 million by 2050. Parkinson’s affects about 145,000 and Huntington’s more than 7,000.
Felodipine is also called by various brand names, including Plendil, Cardioplen XL, Folpik XL, Vascalpha and Neofel XL.
https://www.thelondoneconomic.com/lifestyle/younger-people-with-depression-also-more-prone-to-dementia/21/03/
