Rugonersen, a UBE3A-ATS-Targeting Antisense Oligonucleotide, Shows Promising Safety and Clinical Signals in Phase 1 Trial for Angelman Syndrome Published in Nature Medicine

Jul 19, 2025 12:01 CST Updated 12:01

Roche

Oncology Drug Research, Development, and Manufacturing

Written by Wang Cong

Editor | Wang Duoyu

Typesetting │ Shuicheng Wen

Angelman Syndrome（Angelman syndrome）, a rare genetic developmental disorder, occurs in approximately one out of 20,000 newborns. Affected children suffer from severe intellectual disability, epileptic seizures, walking and sleeping disorders, as well as mutism.(Some even remain silent throughout their lives.), always with a smile on his face, hence the nickname.

Angelman syndrome is caused by an imprinted gene located on chromosome 15.UBE3AMonogenic genetic diseases caused by mutations or deletions, however, their genetic principles are more complex than typical monogenic genetic diseases. Typically, each gene has two copies.(One from the father, one from the mother), this pair of genes is also called alleles. AndUBE3AThe gene is rather unique, as its copy inherited from the father can be transcribed by its antisense strand into a long chain.UBE3A-ATS is silenced, so only the copy from the mother is expressed. If the copy from the motherUBE3AGene出现问题(Mutation or Deletion), which will lead to Angelman syndrome.

For this complex genetic disorder, there is currently no cure, and the only options are to control epileptic seizures with anti-epileptic drugs, along with physical, speech rehabilitation, and behavioral education.

July 11, 2025, Roche（Roche）The researchers atNature MedicineJournal Published：The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial Research Paper.

The clinical trial met the primary endpoint,RugonersenInAngelman SyndromeIn the treatment ofWith an acceptable safety and tolerability profile. Also showed signs of clinical symptom improvement, these preliminary clinical results supportRugonersen Further Development in the Treatment of Angelman Syndrome.

Rugonersen（RO7248824）Is an antisense oligonucleotide（ASO）Drug, through targeted inhibitionUBE3A-ATS, removing its association with the father's contributionUBE3AThe silencing effect of the gene, thereby restoring expression.

This Phase 1, multicenter, open-label, multidose-escalation clinical trial, named TANGELO, aims to studyRugonersen In children with Angelman syndrome aged 1-12(A total of 61 people, with 33 men and 28 women)Safety and Tolerability in China(Primary Endpoint)and pharmacokinetics(Secondary Endpoint). EvaluationRugonersen The key exploratory endpoint for post-treatment changes was EEG δ wave power.(2-4 Hz)InAndBayley Infant FormulaYulian Scale(Third Edition)AndVineland Adaptive Behavior Scale(Third Edition)in various dimensions.

The results showed that the clinical trial had reached the primary endpoint,Rugonersen With an acceptable safety and tolerability profile.The analysis of exploratory endpoints showed that,Rugonersen Can lead to a dose-dependent partial normalization of Angelman syndrome-related EEG abnormalities and show signals of clinical improvement in core symptoms, exceeding expectations based on natural history data.

Overall, the results of this preliminary clinical trial supportRugonersen Further Development in the Treatment of Angelman Syndrome.

Paper Link：

https://www.nature.com/articles/s41591-025-03784-7

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