Journal Article

Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy

Jeanne-Claire Lesbordes, Carmen Cifuentes-Diaz, Audrey Miroglio, Vandana Joshi, Thierry Bordet, Axel Kahn and Judith Melki

in Human Molecular Genetics

Volume 12, issue 11, pages 1233-1239
Published in print June 2003 | ISSN: 0964-6906
Published online June 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg143
Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy

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Spinal muscular atrophy (SMA) is a recessive autosomal disorder characterized by degeneration of lower motor neurons caused by mutations of the survival motor neuron gene (SMN1). No curative treatment is known so far. Mutant mice carrying homozygous deletion of Smn exon 7 directed to neurons display skeletal muscle denervation, moderate loss of motor neuron cell bodies and severe axonal degeneration. These features, similar to those found in human SMA, strongly suggest the involvement of a dying back process of motor neurons and led us to test whether neurotrophic factors might have a protective role in SMA. We report here the therapeutic benefits of systemic delivery of cardiotrophin-1 (CT-1), a neurotrophic factor belonging to the IL-6 cytokine family. Intra-muscular injection of adenoviral vector expressing CT-1, even at very low dose, improves median survival, delays motor defect of mutant mice and exerts protective effect against loss of proximal motor axons and aberrant cytoskeletal organization of motor synaptic terminals. In spite of the severity of SMA phenotype in mutant mice, CT-1 is able to slow down disease progression. Neuroprotection could be regarded as valuable therapeutic approach in SMA.

Journal Article.  4173 words.  Illustrated.

Subjects: Genetics and Genomics

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