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.Wealso 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.

Motoneuron Transplantation Rescues the Phenotype of SMARD1 (Spinal Muscular Atrophy with Respiratory Distress Type 1) / S. Corti, M. Nizzardo, M. Nardini, C. Donadoni, S. Salani, R. Del Bo, D. Papadimitriou, F. Locatelli, N. Mezzina, F. Gianni, N. Bresolin, G.P. Comi. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 29:38(2009 Sep 23), pp. 11761-11771. [10.1523/JNEUROSCI.2734-09.2009]

Motoneuron Transplantation Rescues the Phenotype of SMARD1 (Spinal Muscular Atrophy with Respiratory Distress Type 1)

S. Corti;M. Nizzardo;M. Nardini;S. Salani;R. Del Bo;D. Papadimitriou;F. Locatelli;N. Bresolin;G.P. Comi
2009-09-23

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.Wealso 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.
SMARD1, Spinal muscular atrophy with respiratory distress type 1; motor neurons; stem cell; teraphy
Settore MED/26 - Neurologia
THE JOURNAL OF NEUROSCIENCE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/70977
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