title: Adenoviral cardiotrophin-1 gene transfer protects pmn mice from progressive motor neuronopathy.
abstract: Cardiotrophin-1 (CT-1), an IL-6-related cytokine, causes hypertrophy of cardiac myocytes and has pleiotropic effects on various other cell types, including motoneurons. Here, we analyzed systemic CT-1 effects in progressive motor neuronopathy (pmn) mice that suffer from progressive motoneuronal degeneration, muscle paralysis, and premature death. Administration of an adenoviral CT-1 vector to newborn pmn mice leads to sustained CT-1 expression in the injected muscles and bloodstream, prolonged survival of animals, and improved motor functions. CT-1-treated pmn mice showed a significantly reduced degeneration of facial motoneuron cytons and phrenic nerve myelinated axons. The terminal innervation of skeletal muscle, grossly disturbed in untreated pmn mice, was almost completely preserved in CT-1-treated pmn mice. The remarkable neuroprotection conferred by CT-1 might become clinically relevant if CT-1 side effects, including cardiotoxicity, could be circumvented by a more targeted delivery of this cytokine to the nervous system.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U.129, Institut Cochin de Génétique Moléculaire, 75014 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Bordet
authors.forename: H
authors.initials: H
authors.lastname: Schmalbruch
authors.forename: B
authors.initials: B
authors.lastname: Pettmann
authors.forename: A
authors.initials: A
authors.lastname: Hagege
authors.forename: L
authors.initials: L
authors.lastname: Castelnau-Ptakhine
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: G
authors.initials: G
authors.lastname: Haase
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D016472:Motor Neuron Disease / Q000235:genetics / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010525:Peripheral Nerves / Q000187:drug effects
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; C092073:cardiotrophin 1