Scholarlink

<p>Angelman syndrome (AS) is a complex neurogenetic disorder characterized by severe global developmental delay, motor dysfunction, and epilepsy, primarily resulting from the lack of functional ubiquitin protein ligase E3A (UBE3A) protein expression in neurons. While current management remains largely symptomatic, the therapeutic landscape for AS is rapidly evolving. Emerging strategies aim to restore <i>UBE3A</i> function through upstream interventions, such as gene replacement therapy or unsilencing of the imprinted paternal allele, which is present but transcriptionally silenced in neurons due to genomic imprinting. This imprinting is mediated by the distal portion of a long non-coding RNA known as the <i>UBE3A-antisense transcript</i> (<i>UBE3A-ATS</i>). This <i>UBE3A-ATS</i> has become a key therapeutic target, with several approaches developed to unsilence the paternal allele, including antisense oligonucleotides (ASOs), CRISPR-based editing, synthetic microRNA, and other modalities. To date, three ASO programs have demonstrated promising signals in early clinical development, with reported improvements in clinical outcomes and electroencephalography (EEG) biomarkers. Given the potential for improved outcomes with early intervention, the inclusion of AS in broader genomic newborn screening programs is currently being explored. An early-intervention approach, or combination of approaches, holds significant promise for transforming the lives of individuals affected by AS with outcomes dependent on their age or genotype.</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

Emerging Therapies for Angelman Syndrome

  • 期刊论文

  • 发表日期：

    2026年7月14日

查看全文
  • Cyril Tychon,
  • Theodora Markati,
  • Serpil Alkan,
  • Laura Vanden Brande,
  • Laurent Servais

摘要

Angelman syndrome (AS) is a complex neurogenetic disorder characterized by severe global developmental delay, motor dysfunction, and epilepsy, primarily resulting from the lack of functional ubiquitin protein ligase E3A (UBE3A) protein expression in neurons. While current management remains largely symptomatic, the therapeutic landscape for AS is rapidly evolving. Emerging strategies aim to restore UBE3A function through upstream interventions, such as gene replacement therapy or unsilencing of the imprinted paternal allele, which is present but transcriptionally silenced in neurons due to genomic imprinting. This imprinting is mediated by the distal portion of a long non-coding RNA known as the UBE3A-antisense transcript (UBE3A-ATS). This UBE3A-ATS has become a key therapeutic target, with several approaches developed to unsilence the paternal allele, including antisense oligonucleotides (ASOs), CRISPR-based editing, synthetic microRNA, and other modalities. To date, three ASO programs have demonstrated promising signals in early clinical development, with reported improvements in clinical outcomes and electroencephalography (EEG) biomarkers. Given the potential for improved outcomes with early intervention, the inclusion of AS in broader genomic newborn screening programs is currently being explored. An early-intervention approach, or combination of approaches, holds significant promise for transforming the lives of individuals affected by AS with outcomes dependent on their age or genotype.