Long-term correction of rat model of Parkinson's disease by gene therapy

Abstract

THE implantation of cells genetically modified to express tyrosine hydroxylase has been proposed for the treatment of Parkinson's disease1. Tyrosine hydroxylase converts tyrosine to L-DOPA and endogenous decarboxylase activity then converts L-DOPA to the neurotransmitter dopamine, which alleviates the symptoms of Parkinson's disease. Immortalized cells have been successfully used as intracerebral vehicles for transgene expression of tyrosine hydroxylase, but the tumorigenic potential of these cells prevents their application in humans1-4. Intracerebral expression of this enzyme has also been achieved using primary cells like skin fibroblasts5-7, but the ameliorating effect on a rat model for Parkinson's disease lasted for only a few weeks. We have found that co-transplantation of cultured myoblasts and myotubes enabled reporter genes to be expressed intracerebrally at high and stable levels8-10. Here we show that the intracerebral transplantation of plasmid-transfected primary muscle cells can substantially reduce for the long-term the asymmetric rotational behaviour in the rat model.