Webinars
Date: September 17, 2026
Time: 11-12pm EDT / 5-6pm CEST
Title: Streamlining Exon-Skipping Antisense Oligonucleotide Therapy Development Via a High-Throughput Approach
Description:
Disease-modifying therapies are available for <5% of the >7000 described rare genetic diseases (RGDs). Antisense oligonucleotides (ASOs) represent a promising precision therapy platform for novel RGD therapies, with a leading approach being ASO-mediated ‘skipping’ of an exon containing a deleterious variant to rescue protein function. However, major challenges in this field are that comprehensive analyses identifying exons amenable to ASO-mediated skipping are non-existent, and patient identification and ASO design remain reactive and slow processes. We therefore sought to proactively identify skippable exons across the genome and design ASO sequences that target these exons, shared as an open-access resource.
Speaker:
Title: Therapeutic potential of ASO-mediated KD in KCNT1 epileptic encephalopathy: 5 years follow-up
Description:
KCNT1-related epileptic encephalopathy, including Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), is a severe neurodevelopmental disorder associated with refractory seizures, profound neurologic impairment, and premature death. Pathogenic KCNT1 variants lead to overactive Slack channels, boosting total neuronal potassium currents by up to 40%, driving cortical hyper-excitability and causing seizures. Intrathecal delivery of an experimental, non-allele-specific, KCNT1-targeting ASO in two patients with KCNT1 p.R474H, led to a significant reduction in seizure frequency and intensity. However, investigational treatment was also associated with development of ventricular enlargement or hydrocephalus in both patients, prompting redirection of goals of care in one patient, and a switch to intra-ventricular ASO dosing in another patient and drawing attention to the therapeutic potential of Slack channel knockdown in KCNT1 epileptic encephalopathy as well as an important potential toxicity of some intrathecal ASOs.
