Research ArticleDrug Discovery

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

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Science Translational Medicine  04 Feb 2015:
Vol. 7, Issue 273, pp. 273ra15
DOI: 10.1126/scitranslmed.aaa3634

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A lung phenotype for LRRK2 inhibitors

Human genetic evidence implicates leucine-rich repeat kinase 2 (LRRK2) as a high-priority drug target for Parkinson’s disease. However, the benefit and risk of inhibiting the kinase activity of LRRK2 is unknown and is currently untested in humans. Using two selective LRRK2 kinase inhibitors, Fuji et al. report a safety liability in nonhuman primates characterized by morphological changes in lung. These results are consistent with observations in mice lacking LRRK2. These safety observations offer a cautionary note for pharmacological modulation of LRRK2 in humans.

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