- Q. Is SMN protein needed throughout life or just in development?
- A. SMN appears to be most important at a specific time in early post-natal development in mouse models.
As the efficacy of restoring SMN protein levels in SMA patients once symptoms are apparent has not been determined, the team generated a mouse model whose SMN gene could be turned on and off, allowing them to investigate the effects of turning on SMN expression at different rimes points during the course of the disease. They found that restoring SMN protein even after disease onset was sufficient to reverse neuromuscular pathology and effect robust rescue of the SMA phenotype. Importantly,the findings also indicated that there was a therapeutic window of opportunity of 4 days, defined by the extent of neuromuscular synapse pathology and the ability of motor neurons to respond to SMN induction, following which restoration of the protein to the organism failed to produce therapeutic benefit. Nevertheless, these results suggest that, even in severe SMA, timely reinstatement of the SMN protein may halt the progression of the disease and serve as an effective post-symptomatic treatment.