Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis

Isao Nagano, Hristelina Ilieva, Mito Shiote, Tetsuro Murakami, Masataka Yokoyama, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

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Abstract

Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on motor neurons both in vitro and in vivo, but has limited efficacy in patients with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were treated by continuous IGF-1 delivery into the intrathecal space of the lumbar spinal cord. We found that the intrathecal administration of IGF-1 improved motor performance, delayed the onset of clinical disease, and extended survival in the G93A transgenic mice. Furthermore, it increased the expression of phosphorylated Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in these mice. Taken together, the results suggest that direct administration of IGF-1 into the intrathecal space may have a therapeutic benefit for ALS.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalJournal of the Neurological Sciences
Volume235
Issue number1-2
DOIs
Publication statusPublished - Aug 15 2005

Fingerprint

Spinal Injections
Amyotrophic Lateral Sclerosis
Somatomedins
Motor Neurons
Transgenic Mice
Spinal Cord
Therapeutics
Mutation
Survival

Keywords

  • Akt
  • Bcl-2
  • ERK
  • Motor neuron
  • SOD1 mutation
  • Spinal cord

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis. / Nagano, Isao; Ilieva, Hristelina; Shiote, Mito; Murakami, Tetsuro; Yokoyama, Masataka; Shoji, Mikio; Abe, Koji.

In: Journal of the Neurological Sciences, Vol. 235, No. 1-2, 15.08.2005, p. 61-68.

Research output: Contribution to journalArticle

Nagano, Isao ; Ilieva, Hristelina ; Shiote, Mito ; Murakami, Tetsuro ; Yokoyama, Masataka ; Shoji, Mikio ; Abe, Koji. / Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis. In: Journal of the Neurological Sciences. 2005 ; Vol. 235, No. 1-2. pp. 61-68.
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