Research ArticleParkinson’s Disease

LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits

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Science Translational Medicine  22 Apr 2020:
Vol. 12, Issue 540, eaav0820
DOI: 10.1126/scitranslmed.aav0820

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Parsing the side effects of LRRK2 inhibitors

Preclinical studies have raised concerns about the safety of LRRK2 inhibitors—developed for treating Parkinson’s disease—specifically regarding lung function. Baptista et al. now report that several different LRRK2 inhibitors induce on-target histopathological changes in the lungs of nonhuman primates. However, they show that these morphological changes were reversible after drug withdrawal and had no effect on pulmonary function as demonstrated by a battery of lung function tests. These findings suggest that LRRK2 inhibitor–induced effects on lung tissue should not prevent the clinical testing of these compounds.

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