The CTNNB1 Connect & Cure and CTNNB1 Foundation, alongside Asociación CTNNB1, CTNNB1 Italia, Association CTNNB1 France, and researchers and clinicians globally are dedicated to finding effective treatments and cures for CTNNB1 syndrome. The syndrome is also characterized by progressive spasticity, which can in some cases cause loss of already achieved motor milestones. Since 2019, they have brought together researchers from different fields and invested in various research efforts to advance the search for treatment solutions for patients with CTNNB1 syndrome. Simons Searchlight serves as an important platform by remotely collecting high-quality, standardized data on the natural history of the disease and making it available to researchers around the world. Conducting genotype-phenotype correlation study and biochemically characterizing the mutations were critical to understand the effects of the patients' mutations and related molecular function to symptoms. Several induced pluripotent stem cells were generated from patient cells, and preclinical mouse models have provided new insights into the molecular downstream effects of CTNNB1 haploinsufficiency. Multiple therapeutic approaches are in the developing, including small molecule treatments, RNA- and DNA-based therapies, AAV9 gene replacement therapy, which entered the manufacturing phase in November 2023. In this article, we summarize the journey of the CTNNB1 community and its organizations, highlight ongoing and future research projects, and outline the available research resources. The vision for the CTNNB1 community is that in the future several therapeutic options will be available that can be customized to every CTNNB1 patient's needs.
Keywords: CTNNB1 syndrome; animal disease models; gene therapy; muscle spasticity; β-catenin.
The Role of Patient Organizations in Driving Research and Treatment for CTNNB1 Syndrome CTNNB1 syndrome is a rare neurodevelopmental disorder that affects the development and maturation of the brain due to changes in the CTNNB1 gene. This gene is responsible for the expression of the beta-catenin protein, which plays an important role in communication between cells and sends signals to other nearby genes that are also important for healthy brain development. Since 2019, the CTNNB1 Foundation and CTNNB1 Connect & Cure organizations have brought together researchers from different fields and invested in various research efforts to advance the search for treatment solutions for patients with CTNNB1 syndrome. To better understand the disease, natural history and genotype-phenotype correlation studies were conducted with biochemical characterization of the mutations. This was crucial to understand the effects of the patients’ mutations and to link molecular function to symptoms. Several cell and animal models were developed that provided valuable information about the disease. Importantly, several therapeutic approaches have also been developed and tested on these models. In November 2023, the CTNNB1 Foundation began production for its first gene therapy program and preparations for the clinical trial. With the same enthusiasm, we expect further treatment solutions to enter clinical trials in the next two to three years. Our common goal is to have a combination of therapeutic approaches available in the future that can be tailored to the individual CTNNB1 patient.
© The Author(s), 2025.