Riluzole attenuates spinal muscular atrophy disease progression in a mouse model.
Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations of the survival motor neuron 1 gene (SMN1). No curative treatment is available. Mutant mice carrying homozygous deletion of Smn exon 7 directed to neurons display a degenerative process of motor neurons similar to that found in human SMA. To test whether riluzole, which exhibits neurotrophic properties, might have a protective role in SMA, mutant mice were treated with it after the onset of the degenerative process. Riluzole improved median survival and exerted a protective effect against aberrant cytoskeletal organization of motor synaptic terminals but not against loss of proximal axons. These results demonstrate that the disease course of SMA can be attenuated after the onset of neuromuscular defects and may warrant further investigation in a therapeutic trial in SMA.
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D017362:Cyclic AMP Response Element-Binding Protein; D003599:Cytoskeleton / Q000648:ultrastructure; D018450:Disease Progression; D017353:Gene Deletion; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000187:drug effects / Q000648:ultrastructure; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000648:ultrastructure; D016601:RNA-Binding Proteins; D019782:Riluzole / Q000494:pharmacology*; D055532:SMN Complex Proteins; D016019:Survival Analysis; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D019782:Riluzole