Juvenile reinstatement of TCF4 in Pitt-Hopkins syndrome model mice reveals a critical window for genetic intervention.

ABSTRACT: Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by haploinsufficiency of TCF4 which encodes transcription factor 4. As PTHS therapeutics advance toward clinical trials, identifying the optimal timing for treatment is crucial. Our previous research demonstrated that restoring TCF4 during embryonic or neonatal stages, corresponding to prenatal or neonatal periods in humans, improved phenotypes in a PTHS mouse model (Kim et al., 2022). However, PTHS diagnosis generally occurs much later, when infants fail to reach developmental milestones and undergo genetic testing. This raises an essential question: can genetic therapeutics initiated at more clinically relevant time points retain effectiveness? Here, we examined whether reinstating TCF4 in juvenile PTHS model mic

SUBMITTER: James LM 

PROVIDER: S-EPMC12776099 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature