Somatic gene therapy in animal models of Parkinson’s disease
Gene therapy in Parkinson’s disease (PD) emerged about 10 years ago but until now, no clinical trials are under way, because most approaches have failed to show long-term therapeutic effects in PD animal models and because safety concerns precluded the use in humans so far. This review tries to give an overview on the development of different strategies in gene therapy in PD animal models and point out new and possibly more successful directions, including the transplantation of neural precursor cells and pig tissue.
KeywordsGene Therapy Tyrosine Hydroxylase Primary Fibroblast Gene Therapy Approach Nondividing Cell
Unable to display preview. Download preview PDF.
- Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, Horellou P (1997) Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioural impairment in a rat model of Parkinson disease. Proc Natl Acad Sci USA 94: 8818–8823.PubMedCrossRefGoogle Scholar
- Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Kriek E, Qi JX, Lone T, Zhang YB, Snyder JA, Wells TH, et al (1992) Survival of implanted fetal dopamine cells and neurological improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327: 1549–1555.PubMedCrossRefGoogle Scholar
- Gage F (1998) Cell therapy. Nature 392: S18–S24.Google Scholar
- Lange K, Youdim M, Riederer P (1992) Neurotoxicity and neuroprotection in Parkinson’s disease. J Neural Transm 38: 27–44.Google Scholar
- Mehler MF, Rozental R, Dougherty M, Spray DC, Kessler JA (1993) Cytokine regulation of neural differentiation of hippocampal progenitor cells. Science 362: 62–65.Google Scholar
- Sautter J, Tseng JL, Braguglia D, Aebischer P, Spenger C, Seiler RW, Widmer HR, Zurn AD (1998) Implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor improve survival, growth and function of dopaminergic grafts. Exp Neurol 149: 230–236.PubMedCrossRefGoogle Scholar
- Speck PG, Simmons A (1991) Divergent molecular pathways of productive and latent infection with a virulent strain of herpes simplex virus type 1. J Virol 65: 4004–4005.Google Scholar
- Ward T, Pipkin PA, Clarkson NA, Stone DM, Minor PD, Almond JW (1994) Decayaccelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO 13: 5070–5074.Google Scholar