However, valproic acid has also serious adverse effects in cell and mice models for SMA [53, 54] pointing again to the need of inhibition of selected HDACs in MNDs, especially in the light of a recent report that the SMN2 gene is differentially regulated by individual HDAC proteins and silencing of HDAC5 and 6 enhances inclusion of an alternatively spliced exon in SMN2 [55]. This evidence concerns the gene SMN2 and proximal spinal muscular atrophy.