Despite the sound epidemiologic and basic science rationales underpinning numerous "disease modification" trials in manifest Parkinson disease, none has convincingly demonstrated that a treatment slows progression.
Rapidly expanding knowledge of the genetic determinants and prodromal features of Parkinson disease now allows realistic planning of prevention trials with initiation of putatively neuroprotective therapies earlier in the disease.
In this article, the authors outline the principles of drug selection for Parkinson disease prevention trials, focused on proof-of-concept opportunities that will help establish a methodological foundation for this fledgling field.
The scientists describe prototypical, relatively low-risk drug candidates for such trials, tailored to specific at-risk populations ranging from pathogenic or gene variant carriers to those defined by prodromal Parkinson disease and α-synucleinopathy. Their proposal includes caffeine, Ibuprofen, Albuterol, Ambroxol.
Finally, the authors review gene-targeted approaches currently in development targeting clinically manifest Parkinson disease for their potential in future prevention trials.