Effect of selective LRRK2 kinase inhibition on nonhuman primate lung-Reference-Cited by-同舟云学术

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

Published:2015-02-04 Issue:273 Volume:7 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Fuji Reina N.¹,Flagella Michael¹,Baca Miriam²,S. Baptista Marco A.³,Brodbeck Jens¹,Chan Bryan K.⁴,Fiske Brian K.³,Honigberg Lee⁵,Jubb Adrian M.²,Katavolos Paula¹,Lee Donna W.¹,Lewin-Koh Sock-Cheng⁶,Lin Tori¹,Liu Xingrong⁷,Liu Shannon¹,Lyssikatos Joseph P.⁴,O’Mahony Jennifer¹,Reichelt Mike²,Roose-Girma Merone⁸,Sheng Zejuan⁹,Sherer Todd³,Smith Ashley⁵,Solon Margaret²,Sweeney Zachary K.⁴,Tarrant Jacqueline¹,Urkowitz Alison³,Warming Søren⁸,Yaylaoglu Murat²,Zhang Shuo⁹,Zhu Haitao⁹,Estrada Anthony A.⁴,Watts Ryan J.⁹

Affiliation:

1. Department of Safety Assessment, Genentech Inc., South San Francisco, CA 94080, USA.

2. Department of Pathology, Genentech Inc., South San Francisco, CA 94080, USA.

3. The Michael J. Fox Foundation for Parkinson’s Research, New York, NY 10018, USA.

4. Department of Discovery Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.

5. Department of Pharmacodynamic Biomarkers, Genentech Inc., South San Francisco, CA 94080, USA.

6. Department of Nonclinical Biostatistics, Genentech Inc., South San Francisco, CA 94080, USA.

7. Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA 94080, USA.

8. Department of Molecular Biology, Genentech Inc., South San Francisco, CA 94080, USA.

9. Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA.

Abstract

LRRK2 kinase inhibitors, under development for Parkinson’s disease, have an effect on type II pneumocytes in nonhuman primate lung, suggesting that pulmonary toxicity may be a critical safety liability.

Funder

The Michael J. Fox Foundation for Parkinson's Research

Genentech Inc.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Reference38 articles.

1. Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology

2. Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease

3. LRRK2 Low-penetrance Mutations (Gly2019Ser) and Risk Alleles (Gly2385Arg)—Linking Familial and Sporadic Parkinson’s Disease

4. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

5. Identification of a Novel LRRK2 Mutation Linked to Autosomal Dominant Parkinsonism: Evidence of a Common Founder across European Populations

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