Adenoviral cardiotrophin-1 gene transfer protects pmn mice from progressive motor neuronopathy

Cardiotrophin-1 (CT-1), an IL-6-related cytokine, causes hypertrophy of car diac myocytes and has pleiotropic effects on various other cell types, incl uding motoneurons. Here, we analyzed systemic CT-1 effects in progressive m otor neuronopathy (pmn) mice that suffer from progressive motoneuronal dege neration, muscle paralysis, and premature death. Administration of an adeno viral CT-1 vector to newborn pmn mice leads to sustained CT-1 expression in the injected muscles and bloodstream, prolonged survival of animals, and i mproved motor functions. CT-1-treated pmn mice showed a significantly reduc ed degeneration of facial motoneuron cytons and phrenic nerve myelinated ax ons. The terminal innervation of skeletal muscle, grossly disturbed in untr eated pmn mice, was almost completely preserved in CT-1-treated pmn mice. T he remarkable neuroprotection conferred by CT-1 might become clinically rel evant if CT-1 side effects, including cardiotoxicity, could be circumvented by a more targeted delivery of this cytokine to the nervous system.