RNA-targeted therapeutic approaches have provided an exciting new treatment for other genetic diseases, and recent successes with anti-sense oligonucleotides (ASOs) in spinal muscular atrophy [31] and Huntington’s disease [32] raise the possibility of reducing tau transcript expression as a therapeutic approach in tauopathies. Given the diverse roles of tau in the human brain, complete knockdown has been approached cautiously, but in many mouse models, complete tau knockout has no overt phenotype, suggesting that reduction of tau expression may not be deleterious and well tolerated [12,33-35]. These data are complemented by findings that tau reduction may also be protective against seizure activity in pre-clinical models [36].
