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. 2022 Nov;66(5):631-638.
doi: 10.1002/mus.27715. Epub 2022 Sep 15.

Alterations in insulin-like growth factor system in spinal muscular atrophy

Ayse Yesbek Kaymaz  1 , Sevgi Kostel Bal  2 , Gamze Bora  1 , Beril Talim  3 , Alev Ozon  4 , Ayfer Alikasifoglu  4 , Haluk Topaloglu  2 , Hayat Erdem Yurter  1
Affiliations

Alterations in insulin-like growth factor system in spinal muscular atrophy

Ayse Yesbek Kaymaz et al. Muscle Nerve. 2022 Nov.

Abstract

Introduction/aims: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease caused by survival motor neuron (SMN) protein deficiency. Insulin-like growth factor-I (IGF-I) is a myotrophic and neurotrophic factor that has been reported to be dysregulated in in vivo SMA model systems. However, detailed analyses of the IGF-I system in SMA patients are missing. In this study, we analyzed the components of the IGF-I system in serum and archived skeletal muscle biopsies of SMA patients.

Methods: Serum IGF-I, IGF binding protein (IGFBP)-3, and IGFBP-5 levels were analyzed in 11 SMA patients and 13 healthy children by immunoradiometric and enzyme-linked immunosorbent assays. The expression of IGF-I, IGF-I receptor, and IGFBP-5 proteins was investigated by immunofluorescence analysis in the archived skeletal muscle biopsies of nine SMA patients, six patients with non-SMA-related neuromuscular disease and atrophic fibers in muscle biopsy, and four controls.

Results: A significant decrease in IGF-I levels (mean ± SD: -1.39 ± 1.46 vs. 0.017 ± 0.83, p = .02) and increase in IGFBP-5 levels (mean ± SD: 2358.5 ± 1617.4 ng/mL vs. 1003.4 ± 274.3 ng/mL, p = .03) were detected in serum samples of SMA patients compared to healthy controls. Increased expression of IGF-I, IGF-I receptor, and IGFBP-5 was detected in skeletal muscle biopsies of SMA patients and non-SMA neuromuscular diseases, indicating atrophy-specific alterations in the pathway.

Discussion: Our findings suggested that the components of the IGF-I system are altered in SMA patients at both the systemic and tissue-specific levels.

Keywords: IGF-I; IGFBP; motor neuron; muscle atrophy; spinal muscular atrophy.

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References

REFERENCES

    1. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet. 1978;15(6):409-413. doi:10.1136/jmg.15.6.409
    1. Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155-165. doi:10.1016/0092-8674(95)90460-3
    1. Farrar MA, Kiernan MC. The genetics of spinal muscular atrophy: Progress and challenges. Neurotherapeutics. 2015;12(2):290-302. doi:10.1007/s13311-014-0314-x
    1. Prior TW, Swoboda KJ, Scott HD, Hejmanowski AQ. Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2. Am J Med Genet. 2004;130A:307-310. doi:10.1002/ajmg.a.30251
    1. Oprea G, Kröber S, McWhorter M, et al. Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science. 2008;320:524-527. doi:10.1126/science.1155085

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