MECP2 and Rett syndrome: Based on animal studies in which IGF-1 and BDNF supplementation therapies improved neuronal developmental, synaptic maturation and plasticity exerted through the key cell-signaling pathways, PI3K/Akt and MAPK in MeCP2 mutant mice (Castro et al., 2013), a clinical trial in 10 Rett syndrome patients showed improvement in social and cognitive ability with recombinant human Insulin-Like Growth Factor 1 supplementation (Pini et al., 2016).