Intraspinal cord delivery of IGF-I mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS

Colin K. Franz, Thais Federici, Jun Yang, Carey Backus, Sang Su Oh, Qingshan Teng, Erin Carlton, Kathie M. Bishop, Mehdi Gasmi, Raymond T. Bartus, Eva L. Feldman, Nicholas M. Boulis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that is characterized by the progressive loss of motor neurons. Patients with ALS usually die from respiratory failure due to respiratory muscle paralysis. Consequently, therapies aimed at preserving segmental function of the respiratory motor neurons could extend life for these patients. Insulin-like growth factor-I (IGF-I) is known to be a potent survival factor for motor neurons. In this study we induced high levels of IGF-I expression in the cervical spinal cord of hSOD1G93A rats with intraspinal cord (ISC) injections of an adeno-associated virus serotype 2 vector (CERE-130). This approach reduced the extent of motor neuron loss in the treated segments of the spinal cord. However, a corresponding preservation of motor function was observed in male, but not female, hSOD1G93A rats. We conclude that ISC injection of CERE-130 has the potential to protect motor neurons and preserve neuromuscular function in ALS.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalNeurobiology of Disease
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2009

Keywords

  • Adeno-associated virus
  • Amyotrophic lateral sclerosis
  • Cell death
  • Gene therapy
  • Insulin-like growth factor-I
  • Motor neuron
  • Motor performance
  • Neurodegeneration
  • Neuroprotection
  • Spinal cord
  • hSOD1 rat

ASJC Scopus subject areas

  • Neurology

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