Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, and long-QT syndrome. TS type I (TSI) is caused by a gain-of-function variant in the *CACNA1C* gene, specifically exon 8A. Previous studies have identified several phenotypes in neurons derived from TSI patients, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction, and persistent expression of exon 8A. To address these issues, researchers developed antisense oligonucleotides (ASOs) to reduce the inclusion of exon 8A in human cells both in vitro and in vivo following transplantation. The ASOs effectively decreased exon 8A inclusion, rescued defects in patient-derived cortical organoids and forebrain assembloids, and improved calcium changes and dendrite retraction in patient neurons. This study demonstrates that suppressing *CACNA1C* exon 8A expression is a potential therapeutic strategy for TSI, highlighting the potential of a multilevel, in vitro and in vivo stem cell model-based approach to identify and develop treatments for neurodevelopmental disorders.Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, and long-QT syndrome. TS type I (TSI) is caused by a gain-of-function variant in the *CACNA1C* gene, specifically exon 8A. Previous studies have identified several phenotypes in neurons derived from TSI patients, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction, and persistent expression of exon 8A. To address these issues, researchers developed antisense oligonucleotides (ASOs) to reduce the inclusion of exon 8A in human cells both in vitro and in vivo following transplantation. The ASOs effectively decreased exon 8A inclusion, rescued defects in patient-derived cortical organoids and forebrain assembloids, and improved calcium changes and dendrite retraction in patient neurons. This study demonstrates that suppressing *CACNA1C* exon 8A expression is a potential therapeutic strategy for TSI, highlighting the potential of a multilevel, in vitro and in vivo stem cell model-based approach to identify and develop treatments for neurodevelopmental disorders.