This week we profile a recent publication in Neurology from Dr. Grace Crotty (pictured, top left) in
the laboratory of Dr. Michael Schwarzchild (bottom right) at Massachusetts General Hospital.
Can you provide a brief overview of your lab’s current research focus?
In Michael Schwarzschild’s lab at the MassGeneral Institute for Neurodegenerative Disease, basic and physician-scientists work closely on research investigating molecular mechanisms in Parkinson’s disease’s (PD) development and progression, and their translational implications. Our research is currently focused on understanding LRRK2 gene function and identifying markers of penetrance in LRRK2 mutation carriers, the leading monogenic cause for PD. This mutation demonstrates incomplete penetrance for PD, suggesting that other genetic or environmental factors modulate the risk of developing PD in these at-risk individuals.
What is the significance of the findings in this publication?
Our study observed that caffeine and its related analytes were lower in individuals with PD than in controls, with a greater difference seen when comparing LRRK2 mutation carriers with PD against carriers without the disease. This finding in LRRK2 mutation carriers suggests that caffeine or its analytes could be a potential marker of resistance to developing PD in these individuals. These results demonstrate an intriguing association between caffeine and the LRRK2 mutation and encourage further research exploring caffeine-related pathways in LRRK2 mutation and PD. Our findings should not change current clinical practice as we do not know whether they reflect causality for PD development in at-risk individuals.
What are the next steps for this research?
We are repeating metabolomic profiling in another well-characterized PD genetic cohort to see if our findings can be replicated and assess their specificity in other PD gene mutation carriers (i.e., Glucocerebrosidase (GBA) mutation carriers). Our lab is also carrying out experiments in LRRK2 mutation models to investigate further some of the observed metabolite- LRRK2 associations.
This work was funded by:
Michael J. Fox Foundation for Parkinson’s Research, the Farmer Family Foundation Initiative for Parkinson’s Disease Research, a Jane & Alan Batkin Research Fellowship, The Edmond J. Safra Fellowship in Movement Disorders, and National Institute of Health (R01NS110879).
