A promising new study led by scientists at the University of Cambridge has discovered a common drug used to treat high blood pressure may also be beneficial for a variety of neurodegenerative diseases, including Parkinson's and dementia. The research has only been verified in animal studies at this time but the scientists are cautiously optimistic it will translate to human subjects.
Repurposing older, already approved drugs for new uses is perhaps one of the more efficient medical research strategies. These drugs have already moved through expensive and onerous trials to establish human safety profiles, so it can be a much faster process to newfound clinical uses.
This new research began by screening existing approved drugs for indications they can induce a process known as autophagy. This natural cellular mechanism is like the body's automated recycling system, clearing out dysfunctional or toxic materials. One of the hallmarks for many neurodegenerative diseases is the build-up of toxic proteins in the brain causing irreversible neuronal damage. In these cases, the body's autophagy mechanism seems to be impaired.
The new study homed in on one drug in particular for its ability to induce autophagy and cross the blood-brain barrier. Felodipine is a common hypertension medication and was originally approved for clinical use in the late 1980s, so it has several decades of long-term human administration proving it is safe.
The researchers tested the efficacy of felodipine to induce autophagy in several different animal models, including mice with Huntington's and Parkinson's, plus a zebrafish model for dementia. The results were extraordinarily positive across all experiments. The drug was effective in inducing autophagy and in enhancing the clearance of toxic proteins across all animal models.
Furthermore, the researchers found that the concentrations of felodipine needed for beneficial effects were relatively similar to those tolerated by humans. This particular discovery is important as prior work repurposing older drugs for new uses has often used concentrations in animal studies that would exceed safe dosing levels in humans.
"This is the first time 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 David Rubinsztein, lead on the study from the University of Cambridge. "As a result, the drug was able to slow down progression of these potentially devastating conditions and so we believe it should be trialed in patients."
Needless to say, it is still early days for the research, and there are enormous volumes of animal research that ultimately are never effectively replicated in humans. However, there are some extra observations to suggest this study could translate into positive human results.
As well as revealing felodipine does concentrate in the brain – which is vital if it is to help induce localized autophagy in neural cells – there have been prior epidemiological studies that found patients using the drug to treat hypertension tend to display lower rates of Parkinson's disease. A large 2014 study of over 60,000 patients found that those taking felodipine exhibited lower rates of Parkinson's disease, suggesting either hypertension increases a person's risk of Parkinson's disease, or, as this new Cambridge study implies, the antihypertensive drug more directly reduces a person's general risk by inducing autophagy.
Rubinsztein and the team are well aware human trials are needed to clarify whether felodipine acts as a neuroprotective agent and hope it will be tested in patients soon.
"This is only the first stage, though," says Rubinsztein. "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."
The new study was published in the journal Nature Communications.
Source: University of Cambridge
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