Human Molecular Genetics. 10(18):1925-1933, SEPTEMBER 1, 2001

PMID: 11555629

Issn Print: 0964-6906

Publication Date: September 1, 2001


Share this on facebook   Share this on Twitter   Share this on LinkedIn   Email this article  



Print

Protective effects of cardiotrophin-1 adenoviral gene transfer on neuromuscular degeneration in transgenic ALS mice

Thierry Bordet;Jeanne-Claire Lesbordes;Saïd Rouhani;Laëtitia Castelnau-Ptakhine;Henning Schmalbruch;Georg Haase;Axel Kahn;

+ Author Information


    loading  Checking for direct PDF access through Ovid

Abstract

Amyotrophic lateral sclerosis (ALS) is mainly a sporadic neurodegenerative disorder characterized by loss of cortical and spinal motoneurons. Some familial ALS cases (FALS) have been linked to dominant mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Transgenic mice overexpressing a mutated form of human SOD1 with a Gly93Ala substitution develop progressive muscle wasting and paralysis as a result of spinal motoneuron loss and die at 5 to 6 months. We investigated the effects of neurotrophic factor gene delivery in this FALS model. Intramuscular injection of an adenoviral vector encoding cardiotrophin-1 (CT-1) in SOD1G93A newborn mice resulted in systemic delivery of CT-1, supplying motoneurons with a continuous source of trophic factor. CT-1 delayed the onset of motor impairment as assessed in the rotarod test. Axonal degeneration was slowed and skeletal muscle atrophy was largely reduced by CT-1 treatment. By monitoring the amplitude of the evoked motor response, we showed that the time-course of motor impairment was significantly decreased by CT-1 treatment. Thus, adenovirus-mediated gene transfer of neurotrophic factors might delay neurogenic muscular atrophy and progressive neuromuscular deficiency in ALS patients.

Related Topics

    Related Articles

        loading  Loading Related Articles