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J Neurochem. 2016 Jan;136(2):351-62. doi: 10.1111/jnc.13269. Epub 2015 Aug 28.

Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy.

Author information

1
Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
2
Institute of Pathophysiology, University Medicine Greifswald, Karlsburg, Germany.
3
Department of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, Germany.
4
Department of Neuroimmunology, Institute for Multiple Sclerosis Research and Hertie Foundation, University Medical Center Göttingen, Göttingen, Germany.
5
Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany.
6
Department of Genetic Epidemiology, University Medical Center Göttingen, Göttingen, Germany.

Abstract

Duchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD. Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11-week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre-clinical long-term studies should be helpful.

KEYWORDS:

Duchenne muscular dystrophy; immunoglobulin G treatment; immunomodulation; mdx mouse model; muscle inflammation; voluntary wheel running

PMID:
26230042
DOI:
10.1111/jnc.13269
[Indexed for MEDLINE]
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