[Gene therapy for Parkinson's disease]

Parkinson's disease is a progressive neurodegenerative disorder whose main histopathological feature is the loss of dopaminergic neurons in the pars compacta of the substantia nigra with secondary striatal dopaminergic insufficiency. Treatment relies on medical therapy, using levodopa and dopaminergic agonists. However, the development of treatment complications, including motor fluctuations and levodopa-induced dyskinesia, led to the development of alternative therapeutical strategies such as deep brain stimulation and gene therapy.

Current gene therapy models for Parkinson's disease have focused on two strategies. The first one is the replacement of biosynthetic enzymes for dopamine synthesis and the second consists in the addition of neurotrophic factors for protection and restoration of dopaminergic neurons.

Neuroprotection and restoration of the nigrostriatal pathway are important issues for future genetic treatment strategies for Parkinson's disease and could include, in addition to neurotrophic factors, genes to prevent apoptosis or detoxify free radical species.