Neural precursor grafts restore motor and non-motor functions in parkinsonian macaques

Cognitive deficits as well as sleep and biological rhythm disorders constitute the non-motor symptoms that significantly impact quality of life in Parkinson′s disease. Few studies have evaluated the impact of cell replacement therapy on non-motor symptoms. Here we implement a multidisciplinary and multiparametric assessment of the therapeutic potential of bilateral grafts of neural precursors in a macaque model of Parkinson disease on both motor and non-motor markers of functional recovery. Integration and survival of grafted cells correlated with robust functional recovery in middle-aged animals. Histological examination showed that grafted NP cells acquired a dopaminergic and serotoninergic fate and promoted the dopaminergic phenotype in the host tissue. These findings point to complex cellular mechanisms underlying the capacity of the grafts to reverse the symptoms. We show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Motor and cognitive recovery and partial circadian rhythm recovery correlated with the degree of graft integration into the host environment as well as with in-vivo levels of striatal dopaminergic innervation and function. Further, our findings suggest that positive benefits from grafts are much more likely to be obtained at early stages of the disease. This study underlines the importance of multidisciplinary assessment in view of clinical translation and provides empirical evidence that integration of neural precursors following transplantation in diverse functional domains of the basal ganglia efficiently restores function at multiple levels in parkinsonian non-human primates.