Emerging disease-modifying therapies for Angelman syndrome: A comprehensive review for pediatric neurologists - PubMed
3 hours ago
- #Angelman syndrome
- #Pediatric neurology
- #Gene therapy
- Angelman syndrome (AS) is a rare neurogenetic disorder caused by loss of functional UBE3A gene expression, affecting 1 in 15,000 live births.
- Symptoms include severe developmental delay, intellectual disability, absent speech, ataxia, epilepsy, and distinctive behavioral features.
- Emerging disease-modifying therapies include antisense oligonucleotide (ASO) therapies, gene replacement approaches, and next-generation strategies like CRISPR-based gene editing.
- ASO therapies (ION582, GTX-102/apazunersen, rugonersen) are the most clinically advanced, with three candidates showing efficacy in Phase 1/2 studies and two advancing to Phase 3 trials.
- Gene replacement therapy (MVX-220) offers potential single-administration treatment but faces challenges in safety, immune responses, and durability.
- Next-generation approaches, including CRISPR activation and epigenetic editing, show preclinical promise but require further development.
- Critical challenges include outcome measurement limitations, genotype stratification, long-term safety monitoring, and ensuring equitable access to therapies.