Gene therapy for Parkinson's disease: recent achievements and remaining challenges


  • M. G. Castro
  • A. David
  • A. Hurtado Lorenzo
  • D. Suwelack
  • E. Millan
  • T. Verakis
  • W. D. Xiong
  • X. P. Yuan
  • P. R. Lowenstein


viral vectors, adenovirus, gene delivery, neurodegenerative disorders, GDNF, Parkinson's disease


Gene therapy is the use of nucleic acids as drugs. Thus, ways had to be developed to deliver this new generation of drugs to target tissues. Various viral and non-viral vectors have been engineered to carry potentially therapeutic nucleic acids into diseased organs or target cells. The brain offers a particular challenge for gene delivery to its constituent cells: it is encased by the skull, separated from the general circulation by the blood brain barrier, and made up of mostly non-dividing cells. The skull limits direct injection of vectors into the brain, the blood brain barrier inhibits the easy entry of vectors injected into the bloodstream, and post mitotic target cells restrict what type of vector can be used to deliver genes to the brain. We will discuss the main challenges faced by gene delivery to the brain, i.e. immune responses to the delivery vectors and therapeutic transgenes and length of duration of the therapy specifically as applied to Parkinson's disease. We will also discuss therapeutic strategies, which could be implemented to treat Parkinson's disease, and the models in which they have been tested.