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Gene Therapy for Parkinson Disease

  1. Chi-Jing Choong,
  2. Hideki Mochizuki

Published Online: 15 NOV 2013

DOI: 10.1002/9780470015902.a0025023



How to Cite

Choong, C.-J. and Mochizuki, H. 2013. Gene Therapy for Parkinson Disease. eLS. .

Author Information

  1. Osaka University Graduate School of Medicine, Osaka, Japan

Publication History

  1. Published Online: 15 NOV 2013


Parkinson disease (PD) presents several features including the relative selective localisation of pathology to the substantia nigra and well-defined motor symptoms caused by dopaminergic degeneration that make it an ideal target for gene therapy. Parallel progress in viral vector systems has made it possible to deliver therapeutic genes directly into the brain with reasonable safety. To date, gene therapy for PD is mainly based on symptomatic approaches that involve enzyme-replacement strategies to restore dopamine (DA) levels or correct the functional perturbation of the basal ganglia caused by DA loss and disease-modifying approaches that depend on delivery of neurotrophic factors and alteration of genetic causes of PD to protect neuronal functions and slow down or even halt disease progression. As supported by the increasing preclinical and clinical evidence, gene therapy may be a promising treatment to relieve the disabling nature of PD.

Key Concepts:

  • Gene therapy for PD focusses on symptomatic approach that involves enzyme-replacement strategy and disease-modifying approach that depends on addition of neurotrophic factors.

  • Intrastriatal expression of genes TH, AADC and GCH, the three key enzymes for DA biosynthesis, can compensate for the decreased levels of DA in PD patients.

  • An approach aiming at modulating STN activity is done by delivering gene GAD, the rate-limiting enzyme for GABA synthesis.

  • Neurotrophic factors including GDNF and NTN have potent trophic activity on dopaminergic neurons and play essential roles in the protection and restoration of neuronal cells.

  • Novel viral vectors are capable of delivering genetic materials to target cells and inducing sustained transgene expression.

  • Four candidates for PD gene therapy including EIAV-AADC-TH-GCH, AAV2-AADC, AAV2-GAD and AAV2-NTN are currently under clinical trial evaluation.


  • gene therapy;
  • Parkinson disease;
  • viral vector;
  • aromatic l-amino acid decarboxylase;
  • glial cell line-derived neurotrophic factor;
  • glutamic acid decarboxylase;
  • neurturin;
  • alpha synuclein;
  • parkin