Imagine a world where a child’s genetic disorder, once considered untreatable, is finally on a path toward real solutions. For families affected by the CTNNB1 syndrome, that future is becoming a reality thanks to the tireless efforts of patient advocacy organizations, researchers, and clinicians.
CTNNB1 syndrome is a rare neurodevelopmental disorder caused by mutations in the CTNNB1 gene, which is essential for brain and muscle development. Children with this condition often experience intellectual disability, motor difficulties, speech delays, and vision impairments. While it was only identified as a distinct genetic disorder in 2012, the recent progress in understanding and developing treatments has been extraordinary.
At the Center for Translational Gene and Cell Therapy (CTGCT), we are committed to supporting research that transforms discoveries into real therapies for rare diseases such as the CTNNB1 syndrome. Several of our scientists are participating in this project. Here’s a look at the progress being made and what’s on the horizon based on the original paper published in Therapeutic Advances in Rare Disease by Miroševič et al.
The Role of Patient Advocacy in Research
Scientific breakthroughs don’t happen in isolation. Since 2019, organizations like the CTNNB1 Foundation and CTNNB1 Connect & Cure, alongside Asociación CTNNB1, CTNNB1 Italia, and Association CTNNB1 France, have played a critical role in advancing research and fostering collaboration. By raising over $3 million, these groups have ensured that scientists can focus on the most impactful studies, accelerating progress toward effective treatments.
A key part of their mission is driving collaboration between geneticists, neurologists, molecular biologists, and biotech companies, in this way creating a network of experts dedicated to understanding and treating CTNNB1 syndrome. In addition, they actively support clinical trials, helping to move potential therapies from the laboratory into real-world applications. Their efforts have already led to significant breakthroughs, from mapping the natural history of CTNNB1 syndrome to pioneering new therapeutic approaches that bring hope to individuals and families worldwide.
Understanding the Disease: A Foundation for Treatment
Before scientists can develop effective therapies, they must first understand how CTNNB1 mutations impact individuals. Research has focused on uncovering the connection between genetic mutations and symptoms, a process known as genotype-phenotype correlation studies. By identifying how specific mutations influence the severity and nature of the disorder, researchers can better predict individual outcomes and tailor treatment approaches.
Identifying key mechanisms of the disease and evaluating possible therapeutic approaches would not be possible without the joint efforts of patient advocacy groups and scientists in driving development of preclinical models, including patient-derived cells and genetically modified mice. These models allow scientists to explore the molecular effects of CTNNB1 mutations and test potential treatments in a controlled environment before advancing to human trials. Additionally, natural history studies play an essential role in tracking how symptoms progress over time, helping researchers determine the best windows for therapeutic intervention.
Together, these research efforts have provided a deeper understanding of the disease and paved the way for multiple treatment strategies aimed at restoring CTNNB1 function in affected individuals.
Promising Treatment Approaches for CTNNB1 Syndrome
The most exciting part of this journey is the emergence of targeted therapies that could change lives. Several approaches are currently in development:
- Gene Therapy (AAV9–based Gene Replacement Therapy) – Delivers a working copy of the CTNNB1 gene to affected cells, with clinical trials expected in the coming year.
- RNA-Based Therapy – Uses antisense oligonucleotides (ASOs) to increase beta-catenin production, potentially improving symptoms without modifying DNA.
- Small Molecule Therapy – Drugs designed to stabilize or enhance beta-catenin levels, targeting the root cause of the disorder.
- DNA Editing (Prime Editing) – A next-generation CRISPR-based approach that could precisely correct CTNNB1 mutations.
Each therapy offers unique benefits and may be tailored to individuals based on their specific genetic mutation and symptom severity. The ultimate goal is to develop personalized treatments that are adapted to each individual’s needs, ensuring the best possible outcomes.
What’s Next? A Future of Personalized Medicine
AAV9-based gene replacement therapy has been successfully manufactured, and clinical trials are expected to begin within this year with high hopes for CTNNB1 individuals and caregivers.
At CTGCT, we believe that translational research is the bridge between discovery and treatment. The journey of the CTNNB1 community is a powerful example of how patient advocacy, scientific innovation, and collaboration can lead to life-changing solutions for rare diseases.
As research progresses, we invite scientists, clinicians, and families to stay engaged and support these efforts. Together, we can turn today’s research into tomorrow’s cure.
If you find this story interesting and would like to be part of a team working towards the translation of treatment for the CTNNB1 syndrome and other rare diseases, do not hesitate to contact us. The CTGCT is expanding its team this year!