Gene therapy for Parkinson’s disease: review and update

Abstract

Gene transfer technology is under exploration to find therapies for the treatment of Parkinson’s disease (PD) and other neurodegenerative disorders. The technology of genetic transfer can also be used as a neurobiological tool to understand the role of various genes in animal models of neurodegeneration. We describe the general approaches to gene therapy for neurodegeneration, with specific attention to commonly used methodologies. Current gene therapy models for PD are then described in two parts: genetic transfer of the biosynthetic enzymes for dopamine synthesis, and genetic transfer of the genes encoding neurotrophic factors protective for dopaminergic neurones. Future strategies for the genetic treatment of PD, such as the introduction of genes to prevent apoptosis or to detoxify free radical species are also discussed. Limitations of current approaches, such as the length and regulation of transgene expression, as well as strategies to overcome those limitations, are emphasised where possible. Gene therapy remains a promising but as yet theoretical approach to the treatment of PD in humans. However, current results in animal models predict eventual therapeutic applications.

• aromatic L-amino acid decarboxylase
• brain-derived neurotrophic factor
• gene therapy
• glial cell line-derived neurotrophic factor
• GTP cyclohydrolase 1
• tyrosine hydroxylase