Long-term phenotypic correction of rodent hemiparkinsonism by gene therapy using genetically modified myoblasts

Rat myoblasts were genetically modified to express tyrosine hydroxylase (TH) and produce dopamine in culture. Implanting TH gene-transfected myoblasts into the denervated striatum of 6-OHDA-lesioned rats significantly decreased rotational asymmetry by 50 to approximately 60%. Improvement persisted for up to 13 months. Genetically modified cells could survive and express transgene in the striatum as demonstrated by RT-PCR and immunohistochemical stain-ing. The dopamine content in the striatum tissue of the gene therapy group recovered to 49% of the normal level and was 25-fold higher than that of a control group receiving parental cells. Neither tumor formation nor immunorejection was observed in this study. These results show that myoblasts may be useful as gene carriers for ex vivo gene therapy in the CNS. Gene Therapy (2000) 7, 445-449.