December 23, 2025

@michaelokun

Could LRRK2 be a hidden switch in Parkinson’s even beyond genetic forms of the disease? Disease modifying means a therapy that slows or alters the underlying biology of Parkinson’s, rather than just treating symptoms. Lang and colleagues describe in a new paper in Movement Disorder that LRRK2 biology may help drive Parkinson’s even in folks who do not carry LRRK2 mutations. Key points: - LRRK2 activity appears increased not only in genetic LRRK2 Parkinson’s, but also in many cases of sporadic Parkinson’s. - Hyperactive LRRK2 disrupts lysosomal and autophagy pathways which are central to alpha synuclein handling and neuronal survival. - Preclinical and early human studies suggest LRRK2 inhibitors can normalize these pathways and may possibly slow neurodegeneration. My take: It is so important we pay attention to genetics and genetic forms of Parkinson’s disease. Here are 5 points that resonated w/ me about this paper: 1- Most Parkinson’s is not caused by a single gene, however shared biology still matters. 2- LRRK2 can be overactive even when no LRRK2 mutation is present. 3- Environmental exposures, inflammation and oxidative stress may turn up LRRK2 activity. 4- Blocking LRRK2 in models seems to improve lysosome function and reduces alpha synuclein buildup. 5- Ongoing clinical trials are testing whether targeting LRRK2 can slow Parkinson’s for a broader group of folks, not just those w/ the less common inherited mutations. https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.70100 #parkinson #michaelokun #fixelinstitute