Value of ASO-mediated Restoration of UNC13A Function to Impact Cognition in ALS-FTD

  • First in vivo evidence that prevention of UNC13A cryptic splicing can modify disease-relevant biology, validating UNC13A cryptic exon as a therapeutically actionable target in ALS-FTD
  • Why restoration of UNC13A may be sufficient under certain disease context to move the needle clinically, and how to think about targeting individual cryptic exon versus correcting multiple targets
  • The critical importance of early intervention, with data supporting delivery before irreversible neuronal loss to maximise therapeutic benefit
  • The need for a companion biomarker strategy to guide patient selection and timing in clinical trials, ensuring the right patients receive treatment at the right stage