A study from Encoded Therapeutics suggested that a medicine commonly used to reduce gene-therapy immune responses could also reduce effectiveness. In a Dravet syndrome gene-therapy trial, most of the 21 children received steroids, and higher-dose participants additionally received sirolimus. The analysis is aimed at a key gene therapy challenge: balancing immune suppression against preserving therapeutic expression in the CNS. The report indicates a relationship between the use of immune-modulating regimens and changes in treatment outcomes, raising questions about how to optimize supportive immunosuppression strategies. Encoded’s approach targets SCN1A expression restoration in inhibitory interneurons using an AAV-based platform. The trial design included different immune-suppression regimens to manage capsid- or vector-related risks. The new findings add to an emerging evidence base on how to optimize immunomodulation in CNS gene therapy programs without undermining durability and seizure control.