TY - JOUR AU - Corti, Stefania AU - Nizzardo, Monica AU - Nardini, Martina AU - Donadoni, Chiara AU - Salani, Sabrina AU - Ronchi, Dario AU - Saladino, Francesca AU - Bordoni, Andreina AU - Fortunato, Francesco AU - Del Bo, Roberto AU - Papadimitriou, Dimitra AU - Locatelli, Federica AU - Menozzi, Giorgia AU - Strazzer, Sandra AU - Bresolin, Nereo AU - Comi, Giacomo P. T1 - Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy PY - 2008/10/01/ AB - Spinal muscular atrophy (SMA), a motor neuron disease (MND) and one of the most common genetic causes of infant mortality, currently has no cure. Patients with SMA exhibit muscle weakness and hypotonia. Stem cell transplantation is a potential therapeutic strategy for SMA and other MNDs. In this study, we isolated spinal cord neural stem cells (NSCs) from mice expressing green fluorescent protein only in motor neurons and assessed their therapeutic effects on the phenotype of SMA mice. Intrathecally grafted NSCs migrated into the parenchyma and generated a small proportion of motor neurons. Treated SMA mice exhibited improved neuromuscular function, increased life span, and improved motor unit pathology. Global gene expression analysis of laser-capture-microdissected motor neurons from treated mice showed that the major effect of NSC transplantation was modification of the SMA phenotype toward the wild-type pattern, including changes in RNA metabolism proteins, cell cycle proteins, and actin-binding proteins. NSC transplantation positively affected the SMA disease phenotype, indicating that transplantation of NSCs may be a possible treatment for SMA. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI35432 VL - 118 IS - 10 UR - https://doi.org/10.1172/JCI35432 SP - 3316 EP - 3330 PB - The American Society for Clinical Investigation ER -