Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

Summary

The goal of this first in human, phase I/II clinical trial is to evaulate the safety, tolerability, and preliminary efficacy of AAV9 mediated gene replacement therapy (Urbagen) in paediatric patients with CTNNB1 neurodevelopmental disorder. The main questions it aims to answer are: * Is the gene therapy with Urbagen safe and well tolerated? * Does the gene therapy improve motor function, cognitive function, behavior, sleep, and/or quality of life? Participants will: * Undergo screening assessments to ensure eligibility. * Recieve a single dose of gene therapy via bilateral intracerebroventricular administration. * Recieve prophylactic immunosuppresants (methylprednisolone, sirolimus). * Attend follow-up visits for safety monitoring and clinical assessments over the course of three years.

Timeline

Start

2025-11-01

Primary completion

2032-12-31

Completion

2032-12-31

Publications

• Background Zakelj N, Gosar D, Mirosevic S, Sanders SJ, Ljungdahl A, Kohani S, Huang S, Leong LI, An Y, Teo MJ, Moultrie F, Jerala R, Lainscek D, Forstneric V, Susjan P, Lisowski L, Perez-Iturralde A, Mrak JO, Chan HYE, Osredkar D. Genotypic, functional, and phenotypic characterization in CTNNB1 neurodevelopmental syndrome. HGG Adv. 2025 Oct 9;6(4):100483. doi: 10.1016/j.xhgg.2025.100483. Epub 2025 Jul 18.
• Background Mirosevic S, Khandelwal S, Amerson E, Parks E, Parks M, Cochran L, Gonzalez Hernandez A, Ferraro M, Lisowski L, Perez-Iturralde A, Chung W, Jacob MH, Zakelj N, Lainscek D, Forstneric V, Susjan P, Maruna M, Jerala R, Osredkar D. Paving the way toward treatment solutions for CTNNB1 syndrome: a patient organization perspective. Ther Adv Rare Dis. 2025 Feb 12;6:26330040251318355. doi: 10.1177/26330040251318355. eCollection 2025 Jan-Dec.
• Background Mirosevic S, Khandelwal S, Susjan P, Zakelj N, Gosar D, Forstneric V, Lainscek D, Jerala R, Osredkar D. Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature. Int J Mol Sci. 2022 Oct 19;23(20):12564. doi: 10.3390/ijms232012564.
• Background Parichha A, Datta D, Singh A, Talwar I, Yadav S, Bose M, Suresh V, Mirosevic S, Zakelj N, Gosar D, Osredkar D, Tole S. An evolutionarily conserved role for CTNNB1/beta-CATENIN in regulating the development of the corpus callosum. iScience. 2025 Aug 9;28(9):113335. doi: 10.1016/j.isci.2025.113335. eCollection 2025 Sep 19.
• Background Arkar Silan U, Trebse A, Kovac J, Rogac M, Troha Gergeli A, Sket R, Bregant T, Neubauer D, Peterlin B, Osredkar D. Unravelling genetic etiology of cerebral palsy: findings from a Slovenian pediatric cohort. Front Neurol. 2025 Jul 23;16:1615449. doi: 10.3389/fneur.2025.1615449. eCollection 2025.
• Background Groselj U, Kavcic M, Drole Torkar A, Kafol J, Lainscek D, Jerala R, Sever M, Zver S, Sersa G, Cemazar M, Strojan P, Groselj A, Zerjav Tansek M, Mirosevic S, Ivancan S, Prelog T, Gosar D, Orazem Mrak J, Mlinaric M, Bertok S, Kovac J, Kodric J, Battelino S, Pokorn M, Ihan A, Jazbec J, Battelino T, Osredkar D. Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia. Orphanet J Rare Dis. 2025 Jun 5;20(1):279. doi: 10.1186/s13023-025-03828-8.

Drugs

Indications