Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model

Brain Res. 2000 Dec 15;886(1-2):82-98. doi: 10.1016/s0006-8993(00)02915-2.


During the last few years, recombinant viral vectors derived from adenovirus (Ad), adeno-associated virus (AAV) or lentivirus (LV) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. In recent experiments, in the rat model of Parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (GDNF) at biologically relevant levels in the nigrostriatal system. Injection of the GDNF encoding vectors into either striatum or substantia nigra thus makes it possible to obtain a regionally restricted over-expression of GDNF within the nigrostriatal system that is sufficient to block the toxin-induced degeneration of the nigral dopamine neurons. Injection of GDNF vectors in the striatum, in particular, is effective not only in rescuing the cell bodies in the substantia nigra, but also in preserving the nigrostriatal projection and a functional striatal dopamine innervation in the rat Parkinson model. Long-term experiments using AAV-GDNF and LV-GDNF vectors show, moreover, that sustained GDNF delivery over 3-6 months can promote regeneration and significant functional recovery in both 6-OHDA-lesioned rats and MPTP-lesioned monkeys. The impressive efficacy of the novel AAV and LV vectors in rodent and primate Parkinson models suggests that the time may now be ripe to explore these vector systems as tools for neuroprotective treatments in patients with Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Cell Survival / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Dependovirus / genetics
  • Disease Models, Animal
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor
  • Haplorhini
  • Inflammation / etiology
  • Inflammation / immunology
  • Lentivirus / genetics
  • Microinjections
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / administration & dosage*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Oxidopamine
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / therapy*
  • Rats
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Treatment Outcome


  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Oxidopamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine