We recently collected evidences on an inhibitory effect of the triple combination drug ETI (Elexacaftor, Tezacaftor and Ivacaftor) on the enzyme that converts dihydroceramides (dHCer) into ceramides (Cer) along the de-novo synthetic pathway of sphingolipids. This enzyme is the delta-4 sphingolipid desaturase (DEGS). Based on our results, both published and preliminary, we demonstrate that the molecule responsible for the effect is Tezacaftor and that the inhibition occurs at concentrations that are lower than those observed in the plasma of CF patients treated with ETI. DEGS malfunctioning and subsequent dHCer accumulation is known to cause impairment in the development of both peripheral (PNS) and central nervous systems (CNS), mostly due to a derangement in myelin formation and maintenance. We thus hypothesize that the use of ETI during pregnancy and in the early phases of human development might be potentially at risk to develop alterations of the physiological myelination process. To rule out our concerns, we propose an animal study mimicking, in naïve CD1 mice, the exposure to ETI occurring during human pregnancy, birth and throughout the early stages of development. We will administer ETI in food, at the same pro kilo dose regimen used in clinical practice, to pregnant mothers, before and throughout the pregnancy and for the first three months after mice's birth. During this timeframe, that covers the whole development from in utero to adult individuals, we will perform a set of molecular, in-vivo, and ex-vivo investigations. The aim of our project is to uncover possible alterations linked to the development of the CNS and PNS, that might result in pathological phenotypes later in life. To this purpose, we will also track a specific marker of DEGS1-related hypomyelination and other markers related to PNS myelin impairment. Moreover, since individuals with malfunctioning DEGS frequently develop epilepsy, we will also specifically assess this aspect for ETI exposure.