Motoneuron transplantation rescues the phenotype of SMARD1 (spinal muscular atrophy with respiratory distress type 1).
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.
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, Istituto di Ricovero e Cura a Carattere Scientifico Foundation Ospedale Maggiore Policlinico, Italy.
Stefania
S
Corti
Monica
M
Nizzardo
Martina
M
Nardini
Chiara
C
Donadoni
Sabrina
S
Salani
Roberto
R
Del Bo
Dimitra
D
Papadimitriou
Federica
F
Locatelli
Nicoletta
N
Mezzina
Francesca
F
Gianni
Nereo
N
Bresolin
Giacomo P
GP
Comi
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D055495:Neurogenesis; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010641:Phenotype; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy / Q000601:surgery*; D013234:Stem Cells / Q000502:physiology
D016207:Cytokines; D018696:Neuroprotective Agents