Motoneuron transplantation rescues the phenotype of SMARD1 (Spinal Muscular Atrophy with Respiratory Distress type 1)

Stefania Corti, Monica Nizzardo, Martina Nardini, Chiara Donadoni, Sabrina Salani, Roberto Del Bo, Dimitra Papadimitriou, Federica Locatelli, Nicoletta Mezzina, Francesca Gianni, Nereo Bresolin, Giacomo P. Comi

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal form of infantile motoneuron disease. There is currently no effective treatment, although motor neuron replacement is a possible therapeutic strategy. We transplanted purified motor neurons into the spinal cord of nmd mice, an animal model of SMARD1. We also administered pharmacological treatment targeting the induction of axonal growth toward skeletal muscle target. At the end stage of the disease, donor-derived motor neurons were detected in the nmd anterior horns, extended axons into the ventral roots, and formed new neuromuscular junctions. These data correlated with improved neuromuscular function and increased life spans. The neuroprotective effect was associated with a reduction in proinflammatory molecules in treated spinal cords. This is the first report that functional restoration of motor units with transplanted motoneurons is feasible in an animal model of a human motoneuron disease, opening up new possibilities for therapeutic intervention.

Original languageEnglish
Pages (from-to)11761-11771
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number38
DOIs
Publication statusPublished - Sep 23 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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