The objective of this study was to evaluate the pathology time course of the LRRK2 knockout rat model of PD at 1-, 2-, 4-, 8-, 12-, and 16-months of age. The evaluation consisted of histopathology and ultrastructure examination of peripheral organs, hematology, serum, and urine analysis. It was found that renal and possibly lung and liver abnormalities progress with age in LRRK2 knockout rats. The characterization of LRRK2 knockout rats may prove to be extremely valuable in understanding potential safety liabilities of LRRK2 kinase inhibitor therapeutics for treating PD.
Authors: Marco A. S. Baptista, Kuldip D. Dave, Mark A. Frasier, Todd B. Sherer, Melanie Greeley, Melissa J. Beck, Julie S. Varsho, George A. Parker, Cindy Moore, Madeline J. Churchill, Charles K. Meshul, Brian K. Fiske