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

Authors

  • M. Corbo,

    1. Department of Neurology and Lab. Neuroscience, ‘Dino Ferrari’ Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
    2. NEuroMuscular Omnicentre (NEMO), Fondazione Serena, Milan, Italy
    Search for more papers by this author
  • C. Lunetta,

    1. Department of Neurology and Lab. Neuroscience, ‘Dino Ferrari’ Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
    2. NEuroMuscular Omnicentre (NEMO), Fondazione Serena, Milan, Italy
    Search for more papers by this author
  • P. Magni,

    1. Department of Endocrinology, Pathophysiology and Applied Biology, University of Milan, Italy
    2. Centre of Excellence on Neurodegenerative Diseases, Milan, Italy
    Search for more papers by this author
  • E. Dozio,

    1. Department of Human Morphology and Biomedical Sciences ‘Città Studi ’, University of Milan, Italy
    Search for more papers by this author
  • M. Ruscica,

    1. Department of Endocrinology, Pathophysiology and Applied Biology, University of Milan, Italy
    2. Centre of Excellence on Neurodegenerative Diseases, Milan, Italy
    Search for more papers by this author
  • L. Adobbati,

    1. Department of Neurology and Lab. Neuroscience, ‘Dino Ferrari’ Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
    Search for more papers by this author
  • V. Silani

    1. Department of Neurology and Lab. Neuroscience, ‘Dino Ferrari’ Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
    2. Centre of Excellence on Neurodegenerative Diseases, Milan, Italy
    Search for more papers by this author

M. Corbo, NEuroMuscularOmnicentre (NEMO), Fondazione Serena, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore, 3, 20162 Milano, Italy (tel.: +390291433733; fax: +3902914337200; e-mail: massimo.corbo@centrocliniconemo.it).

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.

Ancillary