Efficient Expression of Igf-1 from Lentiviral Vectors Protects In Vitro but Does Not Mediate Behavioral Recovery of a Parkinsonian Lesion in Rats

Hum Gene Ther. 2015 Nov;26(11):719-33. doi: 10.1089/hum.2015.016. Epub 2015 Oct 1.


Gene therapy approaches delivering neurotrophic factors have offered promising results in both preclinical and clinical trials of Parkinson's disease (PD). However, failure of glial cell line-derived neurotrophic factor in phase 2 clinical trials has sparked a search for other trophic factors that may retain efficacy in the clinic. Direct protein injections of one such factor, insulin-like growth factor (IGF)-1, in a rodent model of PD has demonstrated impressive protection of dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity. However, protein infusion is associated with surgical risks, pump failure, and significant costs. We therefore used lentiviral vectors to deliver Igf-1, with a particular focus on the novel integration-deficient lentiviral vectors (IDLVs). A neuron-specific promoter, from the human synapsin 1 gene, excellent for gene expression from IDLVs, was additionally used to enhance Igf-1 expression. An investigation of neurotrophic effects on primary rat neuronal cultures demonstrated that neurons transduced with IDLV-Igf-1 vectors had complete protection on withdrawal of exogenous trophic support. Striatal transduction of such vectors into 6-OHDA-lesioned rats, however, provided neither protection of dopaminergic substantia nigra neurons nor improvement of animal behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / genetics*
  • Lentivirus / genetics
  • Nerve Growth Factors / therapeutic use*
  • Neurons / cytology
  • Oxidopamine
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Transduction, Genetic


  • Nerve Growth Factors
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • Oxidopamine