Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy

摘要: Spinal muscular atrophy (SMA) is a common neuromuscular disorder in humans. In fact, it the most frequently inherited cause of infant mortality, being result mutations survival motor neuron 1 (SMN1) gene that reduce levels SMN protein. Restoring protein individuals with SMA perceived to be viable therapeutic option, but efficacy such strategy once symptoms are apparent has not been determined. We have generated mice harboring an inducible Smn rescue allele and used them model investigate effects turning on expression at different time points during course disease. even after disease onset was sufficient reverse pathology effect robust phenotype. Importantly, our findings also indicated there window opportunity from P4 through P8 defined by extent synapse ability neurons respond induction, following which restoration organism failed produce benefit. Nevertheless, results suggest severe SMA, timely reinstatement may halt progression serve as effective postsymptomatic treatment.