rhIGF-I for the Treatment of Neuromuscular Disorders

  • V. Silani
  • A. Brioschi
  • A. Sampietro
  • A. Ciammola
  • A. Pizzuti
  • G. Scarlato


Type I insulin-like growth factor-I (IGF-I) receptors are widely distributed throughout the nervous system, suggesting an important role for IGF-I in the growth, development, and maintenance of the central nervous system (CNS). This, in part, has been the stimulus for extensive studies on the actions of IGF-I on muscle and in the CNS. In vitro, IGF-I induces differentiation of muscle cells, prevents myoblast apoptosis and promotes survival of several neuronal types. Furthermore, IGF-I has been shown to stimulate In vitro the proliferation of neuronal progenitor cells and to increase the survival of both neurons and oligodendrocytes. In vivo, IGF-I has profound effects on neuronal and skeletal muscle development including increases in motor neuron sprouting, rate of neuronal recovery after injury, and muscle mass [1]. This pre-clinical evidence suggests that IGF-I may have beneficial effects in pathological conditions characterized by motor neuron loss, denervation, and skeletal muscle atrophy. Recently, the efficacy of recombinant human IGF-I (rhIGF-I) has been studied in patients with amyotrophic lateral sclerosis, post-polio syndrome and myotonic dystrophy. In addition, indirect data from one clinical study suggested that IGF-I may mediate the clinical benefit provided by prednisone in the treatment of Duchenne muscular dystrophy.


Amyotrophic Lateral Sclerosis Motor Neuron Duchenne Muscular Dystrophy Amyotrophic Lateral Sclerosis Patient Duchenne Muscular Dystrophy 
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  1. 1.
    D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13: 227–255PubMedCrossRefGoogle Scholar
  2. 2.
    Radunovic A, Leigh PN on behalf of the European Familial ALS group (1996) Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: correlation between genotype and clinical features. J Neurol Neurosurg Psychiatry 61: 565–572Google Scholar
  3. 3.
    Appel SH (1981) A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 10: 499–505PubMedCrossRefGoogle Scholar
  4. 4.
    Kerkhoff H, Hassan SM, Troost D, Van Etten RW, Veldman H, Jennekens FGI (1994) Insulin-like and fibroblast growth factors in spinal cords, nerve roots and skeletal muscle of human controls and patients with amyotrophic lateral sclerosis. Acta Neuropathol 87: 411–421PubMedCrossRefGoogle Scholar
  5. 5.
    Braunstein GD, Reviczky AL (1987) Serum insulin-like growth factor-I levels in amy-otrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 50: 792–794PubMedCrossRefGoogle Scholar
  6. 6.
    Dore S, Kreiger C, Kar S, Quirion R (1996) Distribution and levels of insulin-like growth factor (IGF-I and IGF-II) and insulin receptor binding sites in the spinal cords of amyotrophic lateral sclerosis ( ALS) patients. Mol Brain Res 41: 128–133Google Scholar
  7. 7.
    Adem A, Ekblom J, Gillberg P-G (1994) Growth factor receptors in amyotrophic lateral sclerosis. Mol Neurobiol 9: 225–231PubMedCrossRefGoogle Scholar
  8. 8.
    Bensimon G, Lacomblez L, Meininger V, and the ALS/Riluzole Study Group (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 330: 585–590Google Scholar
  9. 9.
    Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V for the Amyotrophic Lateral Sclerosis/Riluzole Study Group II (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 347: 1425–1431Google Scholar
  10. 10.
    Appel V, Stewart SS, Smith GR, Appel SH (1987) A rating scale for amyotrophic lateral sclerosis: description and preliminary experience. Ann Neurol 22: 328–333PubMedCrossRefGoogle Scholar
  11. 11.
    Lange DJ, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, Lai EC, Murphy MF, Natter HM, Norris FH, Rudnicki S, and the North American ALS/IGF-I Study Group (1996) Recombinant human insulin-like growth factor-I in ALS: description of a double-blind, placebo-controlled study. Neurology 47 [Suppl 2]: S93–S95Google Scholar
  12. 12.
    Lai EC, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, Murphy MF, Natter HM, Norris FH, Rudnicki SA, and the North America ALS/IGF-I Study Group (1997) Effect of recombinant human insulin-like growth factor I (rhIGF-I) on progression of amy-otrophic lateral sclerosis: a placebo-controlled study. Neurology (in press)Google Scholar
  13. 13.
    Borasio GD, De Jong JMBV, Emile J, Guiloff R, Jerusalem F, Leigh N, Murphy M, Robberecht W, Silani V, Wokke J, and the European ALS/IGF-I study group (1996) Insulin-like growth factor-I in the treatment of amyotrophic lateral sclerosis: Results of the European multicenter, double-blind, placebo-controlled trial. J Neurol [Suppl 2]: S26Google Scholar
  14. 14.
    Leigh N, and The North American and European ALS/IGF-I study groups (1997) The treatment of ALS with recombinant human insulin-like growth factor I (rhIGF-I): pooled analysis of two clinical trials. Neurology 48: A217Google Scholar
  15. 15.
    Sharma KR, Kent-Braun J, Mynhier MA, Weiner MW, Miller G (1994) Excessive muscular fatigue in the postpoliomyelitis syndrome. Neurology 44: 642–646PubMedGoogle Scholar
  16. 16.
    Miller RG, Gelinas DF, Kent-Braun J, Dobbins T, Dao H, Dalakas M (1997) The effect of recombinant insulin like growth factor 1 (rhIGF-l) upon exercise-induced fatigue and recovery in patients with post-polio syndrome. Neurology 48: A217Google Scholar
  17. 17.
    Pizzuti A, Friedman DL, Caskey CT (1993) The myotonic dystrophy gene. Arch Neurol 50: 1173–1179PubMedCrossRefGoogle Scholar
  18. 18.
    Yu KT, Czech MP (1984) The type I insulin-like growth factor receptor mediates the rapid effects of multiplication-stimulating activity on membrane transport system in rat soleus muscle. J Biol Chem 259: 3090–3095PubMedGoogle Scholar
  19. 19.
    Vlachopapadopoulou E, Zachwieja JJ, Gertner JM, Manzione D, Bier DM, Matthews DE, Slonim AE (1995) Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy: A clinical research center study. J Clin Endocrinol Metab 80: 3715–3723Google Scholar
  20. 20.
    Griggs RC, Moxley III RT, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP, Cwik VA, Pandya S, Robison J, King W, Signore L, Schierbecker J, Florence J, Matheson-Burden N, Wilson B (1993) Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology 43: 520–527PubMedGoogle Scholar
  21. 21.
    Rifai Z, Welle S, Moxley III RT, Lorenson M, Griggs RC (1995) Effect of prednisone on protein metabolism in Duchenne dystrophy. Am J Physiol 268 (Endocrinol Metab 31): E67–E74PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1998

Authors and Affiliations

  • V. Silani
    • 1
  • A. Brioschi
    • 1
  • A. Sampietro
    • 1
  • A. Ciammola
    • 1
  • A. Pizzuti
    • 1
    • 2
  • G. Scarlato
    • 1
  1. 1.The Institute of NeurologyUniversity of Milan Medical School and I.R.C.C.S. Maggiore HospitalMilanItaly
  2. 2.C.S.S. Hospital and I.R.C.C.S. San Giovanni RotondoFoggiaItaly

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