Machado-Joseph disease is a
neurodegenerative disease without effective treatment. Patients with
Machado-Joseph disease exhibit significant motor impairments such as
gait ataxia, associated with multiple neuropathological changes including mutant ATXN3 inclusions, marked neuronal loss and
atrophy of the cerebellum. Thus, an effective treatment of symptomatic patients with
Machado-Joseph disease may require cell replacement, which we investigated in this study. For this purpose, we injected cerebellar neural stem cells into the cerebellum of adult
Machado-Joseph disease transgenic mice and assessed the effect on the neuropathology,
neuroinflammation mediators and
neurotrophic factor levels and motor coordination. We found that upon
transplantation into the cerebellum of adult
Machado-Joseph disease mice, cerebellar neural stem cells differentiate into neurons, astrocytes and oligodendrocytes. Importantly, cerebellar neural stem cell
transplantation mediated a significant and robust alleviation of the motor behaviour impairments, which correlated with preservation from
Machado-Joseph disease-associated neuropathology, namely reduction of Purkinje cell loss, reduction of cellular layer shrinkage and mutant ATXN3 aggregates. Additionally, a significant reduction of
neuroinflammation and an increase of
neurotrophic factors levels was observed, indicating that
transplantation of cerebellar neural stem cells also triggers important
neuroprotective effects. Thus, cerebellar neural stem cells have the potential to be used as a cell replacement and neuroprotective approach for
Machado-Joseph disease therapy.