Abstract
In recent years, numerous clinical trials for disease modification in Parkinson’s disease (PD) have failed, possibly because of a “one-size-fits all” approach. Alternatively, a precision medicine approach, which customises treatments based on patients’ individual genotype, may help reach disease modification. Here, we review clinical trials that target genetic forms of PD, i.e., GBA-associated and LRRK2-associated PD. In summary, six ongoing studies which explicitely recruit GBA-PD patients, and two studies which recruit LRRK2-PD patients, were identified. Available data on mechanisms of action, study design, and challenges of therapeutic trials are discussed.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting more than 6 million people worldwide [1]
Since the pathophysiology of PD may be different in different patients, studies should be designed that assess PD treatment on a more individual basis
Early detection of at-risk individuals will be instrumental for early treatments
Summary
Two escalating dose cohorts a see https://www.trialregister.nl/trial/7061 for more information. The kidney has a ~ 6.2-fold higher expression of LRRK2 compared to the brain [52] This is a potential source of peripheral side effects, which can include abnormal accumulations, a-syn aggregations, and impaired autophagy-lysosomal function induced by LRRK2 inhibitors [53,54,55]. Denali has announced a strategic collaboration with a gene diagnostic lab, Centogene, in order to globally identify and recruit LRRK2 mutation carriers, further characterize this genetic subtype, and build a source for patient recruitment for future studies [58] Such strategies of a commercial diagnostic lab in concert with a drug company to offer directed to consumer diagnostic testing is viewed critically by some. Advancing precision medicine will further encourage and support the generation of scientists to develop creative new approaches for detecting, measuring, and analyzing a wide range of biomedical information—including molecular, genomic, cellular, clinical, behavioral, physiological, and environmental parameters [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
