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Felodipine induces autophagy and clears neurotoxic proteins associated with neurodegeneration

last modified May 03, 2019 04:33 PM
New study by the Fleming lab on felodipine in collaboration with CIMR published in Nature Communications

Repurposing is the term given to finding new uses for already marketed drugs. This is an appealing strategy as the safety profiles of the drugs are already known, so they can rapidly be taken into clinical trials in man. However, the challenge of this approach is to find drugs that work in their new indication at the same doses as their existing indication. The Fleming lab use repurposing screens to identify new treatments for neurodegenerative diseases. Their work forms part of a study by Farah Siddiqi and colleagues in David Rubinsztein’s lab at CIMR, recently published in Nature Communications. The paper reports that felodipine, an anti-hypertensive drug, is protective in several animal models of neurodegeneration. Felodipine induces the clearance of neurotoxic proteins and ameliorates disease symptoms in zebrafish and mouse models. Importantly, it does so at plasma concentrations equivalent to those in patients taking the drug for hypertension.

Reference: Siddiqi FH, Menzies FM, Lopez A, Stamatakou E, Karabiyik C, Ureshino R, Ricketts T, Jimenez-Sanchez M, Esteban MA, Lai L, Tortorella MD, Luo Z, Liu H, Metzakopian E, Fernandes HJR, Bassett A, Karran E, Miller BL, Fleming A, Rubinsztein DC. Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing, Nat Commun. 2019 Apr 18;10(1):1817.doi: 10.1038/s41467-019-09494-2.