Free insulin-like growth factor (IGF)-1 and IGF-binding proteins-2 and -3 in serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients

M. Corbo, C. Lunetta, P. Magni, E. Dozio, M. Ruscica, L. Adobbati, V. Silani

Research output: Contribution to journalArticle

Abstract

Background: The insulin-like growth factor-1 (IGF-1) signaling system is regulated by many factors which interact in regulating the bioavailability of IGF-I. In this context, little information is available on free IGF-1, the bioactive form of IGF-1, in amyotrophic lateral sclerosis (ALS). Methods: We investigated the endogenous expression of IGF-1, and two related binding proteins (IGF-binding proteins, IGFBP-2 and BP-3) in serum and cerebrospinal fluid (CSF) of 54 sporadic ALS (sALS) patients. Twenty-five healthy individuals and 25 with other neurological diseases (OND) were used as controls. Total and free IGF-1, and IGFBP-3 levels were detected by immunoradiometric assay (IRMA); IGFBP-2 levels were determined by radioimmunoassay (RIA). Results: Total and free IGF-1, IGFBP-2 and BP-3 serum levels were not significantly different between patients and controls, although in sALS patients free IGF-1 was negatively correlated with ALS-Functional Rating Scale-revised (ALS-FRS-R) score (r = -0.4; P = 0.046) and forced vital capacity (FVC) (r = -0.55; P <0.04). In CSF, free IGF-1 was significantly increased in sALS patients compared with OND (P <0.0001). Conclusions: Though in the serum we did not find significant differences amongst the three groups, IGF-1 bioavailability, represented by the free IGF-1 levels, correlated with disease severity. In the CSF, the significant increment of the free fraction of IGF-1 suggests an up-regulation of the IGF-1 system in the intrathecal compartment of sALS patients. Since IGF-1 is a trophic factor for different tissues, we speculate that high levels of the free IGF-1 in sALS might reflect a physiological defensive mechanism promoted in response to neural degeneration and/or muscle atrophy.

Original languageEnglish
Pages (from-to)398-404
Number of pages7
JournalEuropean Journal of Neurology
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Amyotrophic lateral sclerosis
  • CSF
  • IGF-1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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