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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.
 
 
 Empirical evidence that cell therapy efficiently reverts cognitive and
 clinical motor symptoms in the non-human primate model of Parkinson’s
 disease.
