Viability of long-term gene therapy in the cochlea

Sci Rep. 2014 Apr 22:4:4733. doi: 10.1038/srep04733.

Abstract

Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Cell Survival / genetics
  • Cochlea / metabolism*
  • Deafness / genetics
  • Deafness / therapy
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Gene Transfer Techniques
  • Genes, Reporter
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Male
  • Nerve Growth Factors / genetics
  • Neurotrophin 3 / genetics
  • Organ of Corti / metabolism
  • Organ of Corti / pathology
  • Spiral Ganglion / metabolism
  • Spiral Ganglion / pathology
  • Swine
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Neurotrophin 3