02492nas a2200313   4500000000100000000000100001008004100002260000900043653001200052653001900064653001100083653002200094100002100116700001600137700001600153700002100169700002300190700001600213700002400229700002300253700001800276700002100294700002200315245012400337300001200461490000700473520168400480022001402164       2022                            d  c202210aAnimals10aDrug Discovery10aHumans10aParkinson Disease1 aManuela Cassotta1 aHugo Geerts1 aLise Harbom1 aTiago F. Outeiro1 aIosif Pediaditakis1 aOrly Reiner1 aStefan Schildknecht1 aJens C. Schwamborn1 aJarrod Bailey1 aKathrin Herrmann1 aHelena T. Hogberg00aThe future of Parkinson's disease research: A new paradigm of human-specific investigation is necessary… and possible  a694-7090 v393 aParkinson’s disease (PD) is a complex neurodegenerative condition with a multifactorial origin. To date, approaches to drug discovery for PD have resulted in symptomatic therapies for the motor manifestations and signs associated with neurodegeneration but have failed to identify preventive or curative therapies. This failure mainly originates from the persistence of major gaps in our understanding of the specific molecular basis of PD initiation and progression. New approach methodologies (NAMs) hold the potential to advance PD research while facilitating a move away from ani-mal-based research. We report a workshop involving NAM experts in the field of PD and neurodegenerative diseases, who discussed and identified a scientific strategy for successful, human-specific PD research. We outline some of the most important human-specific NAMs, along with their main potentials and limitations, and suggest possible ways to overcome the latter. Key recommendations to advance PD research include integrating NAMs while accounting for multiple levels of complexity, from molecular to population level; learning from recent advances in Alzheimer’s disease research; increasing the sharing of data; promoting innovative pilot studies on disease pathogenesis; and accessing philanthropic funding to enable studies using novel approaches. Collaborative efforts between different stakeholders, including researchers, clinicians, and funding agencies, are urgently needed to create a scientific roadmap and support a paradigm change towards effective, human-specific research for neurodegenerative diseases without animals, as is already happening in the field of toxicology.  a1868-8551