Leucine-rich repeat kinase 2 allosteric modulators

The present invention relates to binding agents of human Leucine-rich Repeat Kinase 2 (LRRK2). More particular, allosteric modulators of LRRK2 activity have been identified, for targeting LRRK2 in human cells, while leaving LRRK2 subcellular localisation unaffected. Even more specifically, protein binding agents for allosteric modulation of LRRK2 kinase activity are disclosed, comprising immunoglobulin single variable domains (ISVDs) binding to human LRRK2 with nanomolar affinity. The invention thus reveals means and methods for a novel LRRK2 targeting approach through allosteric modulation of its activity for use in treatment of LRRK2-related pathologies, such as Parkinson's disease, as well as for use in detection of LRRK2 in vitro and in vivo, and for use as a diagnostic.