Scholarlink

<p>Early-onset <i>SCN2A</i> developmental and epileptic encephalopathy is caused by <i>SCN2A</i> gain-of-function variants. Here we describe the clinical experience with intrathecally administered elsunersen, a gapmer antisense oligonucleotide targeting <i>SCN2A</i>, in a female preterm infant with early-onset <i>SCN2A</i> developmental and epileptic encephalopathy, in an expanded access program. Before elsunersen treatement, the patient was in status epilepticus for 7 weeks with a seizure frequency of 20–25 per hour. Voltage-clamp experiments confirmed impaired channel inactivation and increased persistent current consistent with a gain-of-function mechanism. Elsunersen treatment demonstrated a favorable safety profile with no severe or serious adverse events reported after 19 intrathecal administrations over 20 months. After administration in combination with sodium channel blockers, status epilepticus was interrupted intermittently and ultimately ceased after continued dosing. A &gt;60% reduction in seizure frequency corresponding to five to seven seizures per hour was observed, which has been sustained during follow-up until the age of 22 months. These data provide preliminary insights on the safety and efficacy of elsunersen in a preterm infant. Additional investigation on the benefits of elsunersen in clinical trials is warranted.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月22日

查看全文
  • Matias Wagner,
  • Géza Berecki,
  • Walid Fazeli,
  • Claudia Nussbaum,
  • Andreas W. Flemmer,
  • Silvana Frizzo,
  • Farina Heer,
  • Florian Heinen,
  • Robert Horton,
  • Henry Jacotin,
  • William Motel,
  • Brian Spar,
  • Christoph Klein,
  • Corinna Siegel,
  • Christoph Hübener,
  • Sophia Stöcklein,
  • Marco Paolini,
  • Martin Staudt,
  • Moritz Tacke,
  • Markus Wolff,
  • Steven Petrou,
  • Marcio Souza,
  • Ingo Borggraefe

摘要

Early-onset SCN2A developmental and epileptic encephalopathy is caused by SCN2A gain-of-function variants. Here we describe the clinical experience with intrathecally administered elsunersen, a gapmer antisense oligonucleotide targeting SCN2A, in a female preterm infant with early-onset SCN2A developmental and epileptic encephalopathy, in an expanded access program. Before elsunersen treatement, the patient was in status epilepticus for 7 weeks with a seizure frequency of 20–25 per hour. Voltage-clamp experiments confirmed impaired channel inactivation and increased persistent current consistent with a gain-of-function mechanism. Elsunersen treatment demonstrated a favorable safety profile with no severe or serious adverse events reported after 19 intrathecal administrations over 20 months. After administration in combination with sodium channel blockers, status epilepticus was interrupted intermittently and ultimately ceased after continued dosing. A >60% reduction in seizure frequency corresponding to five to seven seizures per hour was observed, which has been sustained during follow-up until the age of 22 months. These data provide preliminary insights on the safety and efficacy of elsunersen in a preterm infant. Additional investigation on the benefits of elsunersen in clinical trials is warranted.