LRRK2 and Parkinson disease: However, unlike the splice-switching ASO tested in the present study, inducing partial skipping and inhibition of kinase domain encoding exon 41 (containing the G2019S mutation in familial PD patients), the gapmer strategy causes a significant strong reduction in total LRRK2, which may have a negative impact on the normal activity of LRRK2 protein in the cell.