Can a Blood Pressure Medication Potentially Be Repurposed to Treat Parkinson Disease?

The blood pressure medication felodipine could potentially be “repurposed” as a treatment for neurodegenerative diseases such as Parkinson, Alzheimer, and Huntington diseases, according to findings from a recent study.

Commonly found in most neurodegenerative diseases is the accumulation of aggregate-prone proteins within the cytoplasm of neurons. Such proteins cause pathology “via toxic gain-of-function mechanisms,” wrote the authors. “Thus, the factors regulating their clearance are likely to be important for understanding pathogenesis and developing rational therapeutic strategies.”

The researchers found that felodipine administration in mice at concentrations mimicking those seen in humans can induce autophagy and reduce levels of neurotoxic proteins. This was done by inserting “minipumps” underneath the mice’s skin to enable drug concentration levels similar to those in humans and to keep the levels steady without any major fluctuations.

“This is the first time that we’re aware of that a study has shown that an approved drug can slow the buildup of harmful proteins in the brains of mice using doses aiming to mimic the concentrations of the drug seen in humans,” said David Rubinsztein, BSc, PhD, FRCPath, FMedSci, FRS, a professor of molecular neurogenetics at the University of Cambridge, in an interview.

The study notes that as of now, there are no current treatments for neurodegenerative diseases that use autophagy inducers. While it is possible to start from scratch to develop new experimental drugs for this specific target, it would be more cost-effective and timely to search for candidates among the drugs that are already approved and test them for a new condition.

Overall, the authors were able to conclude that “Our data with this minipump administration suggest that at human-like plasma concentrations, felodipine can induce autophagy in the brains of mice and clear aggregate-prone disease-causing proteins.”

Reference

Siddiqi F, Menzies F, Lopez A, et al. Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing [published online April 18, 2019]. Nature Comm. doi: 10.1038/s41467-019-09494-2.