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Study finds re-purposing blood pressure drug may treat several neurodegenerative conditions

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A team led by Professor David Rubinsztein, UK DRI at Cambridge, have shown that a prescribed drug to treat high blood pressure may be effective in treating conditions such as Parkinson’s disease, Huntington’s disease and forms of dementia.

In a study published today (18th April) in the journal Nature Communications, David’s group and the Cambridge Institute for Medical Research (University of Cambridge) found that Felodipine, a hypertension drug, was able to prevent the build-up of misfolded and potentially neurotoxic proteins in several neurodegenerative conditions.

In healthy individuals, the body uses a mechanism known as autophagy, or ‘self-eating’, to eat and break down toxic materials. However, in neurodegenerative diseases this mechanism is impaired and unable to clear the proteins building up in the brain. There are currently no drugs that can induce autophagy in patients, but in this study, the researchers showed that Felodipine was effective at reducing the build-up of protein aggregates in the genetically modified 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.

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. David Rubinsztein, UK DRI Professor

David continued:

"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.”

The results also support epidemiological studies that have already hinted at a possible link between the drug and reduced risk of Parkinson’s disease. If the drug can induce autophagy in many other neurodegenerative conditions as well, this would open up its clinical application.

The study was funded by Wellcome, the Medical Research Council, Alzheimer’s Research UK, the Alzheimer’s Society, Rosetrees Trust, The Tau Consortium, an anonymous donation to the Cambridge Centre for Parkinson-Plus, Open Targets,  the Guangdong Province Science and Technology Program, with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre.

Reference

Siddiqi, FH et al. Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing. Nature Communications; 18 April 2019; DOI: 10.1038/s41467-019-09494-2

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