Uses
Rugonersen (RG6091; RO7248824) is a locked-nucleic acid (LNA)- modified antisense oligonucleotides (ASOs), and results in reduction of ubiquitin-protein ligase E3A (UBE3A) silencing. Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A, Rugonersen has been used for AS reasearch[1][2].
in vivo
Rugonersen (RO7248824) (24 mg/monkey; i.t.; for 8-85 d) is well tolerated without adverse in-life effects or tissue pathology and produced a robust, long lasting (up to 3 months) paternal reactivation of UBE3A mRNA/protein across key monkey brain regions[1].
Male cynomolgus monkeys[1]
Rugonersen (150 μg; i.c.v.; single dose) selectively and potently reduces UBE3A-ATS, while concomitantly upregulating the UBE3A mRNA and protein[1].
| Animal Model: | Male cynomolgus monkey[1] |
| Dosage: | 24 mg per monkey |
| Administration: | Intrathecal injection; single dose or twice dose with 2 weeks apart; sacrificed at 8, 15, 29, 57, and 85 days after the last dose |
| Result: | Resulted a long duration of action on paternal UBE3A reactivation in NHP brains after IT delivery. |
| Animal Model: | WT and AS Ube3a m-/p+ mice adult mice (10-12 weeks old)[1] |
| Dosage: | 150 μg per mice |
| Administration: | Intracerebroventricular injection; single dose; harvested at 2 weeks post injection |
| Result: | Revealed a steep relationship between UBE3A-ATS knock-down and UBE3A mRNA/protein upregulation, whereby an almost 90% downregulation was needed to achieve a 50% upregulation, respectively. |
References
[1] R Jagasia, et al. Angelman syndrome patient neuron screen identifies a potent and selective clinical ASO targeting UBE3A-ATS with long lasting effect in cynomolgus monkey. bioRxiv, 2022-06-12.
[2] World Health Organization?·?2021: WHO Drug Information.
