Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy - PubMed
5 hours ago
- #antisense oligonucleotide therapy
- #epileptic encephalopathy
- #KCNT1
- Investigates antisense oligonucleotide-mediated KCNT1 knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.
- KCNT1 variants cause overactive Slack channels, increasing neuronal potassium currents by up to 40%, leading to cortical hyperexcitability and seizures.
- Intrathecal delivery of a non-allele-specific KCNT1-targeting antisense oligonucleotide reduced seizure frequency and intensity in two 2-year-old patients.
- Treatment was associated with ventricular enlargement or hydrocephalus in both patients, indicating a potential monitorable toxicity of intrathecal antisense oligonucleotides.