A CTNNB1 Gene Therapy Clinical Trial Has Started

For the first time, a gene therapy developed specifically for CTNNB1 syndrome is being tested in a Phase I/II clinical trial. The first child has already been dosed, showing the treatment has been well tolerated.

CTNNB1 syndrome affects movement, communication, cognition, behaviour, and sleep. In many children, symptoms progress over time, and previously acquired skills such as walking may be lost. Until now, there has been no treatment that addresses the underlying genetic cause of the condition.

Gene therapy is changing this. For the first time, there is a treatment with the potential to change lives. With your support, we can make a meaningful impact on all our children and families affected by this syndrome.

What is the GAIN-CTNNB1 clinical trial?

GAIN-CTNNB1 is a Phase I/II, open-label clinical trial evaluating the safety, tolerability, and preliminary efficacy of URBAGEN, a single-dose, AAV9-based gene replacement therapy for children with CTNNB1 syndrome.

URBAGEN is administered directly into the brain via bilateral intracerebroventricular (ICV) injection in paediatric patients with a genetically confirmed diagnosis of CTNNB1 syndrome.

The primary objective of this early-phase study is to determine whether URBAGEN can be safely and tolerably administered in children. Secondary objectives include the assessment of preliminary clinical and developmental outcomes.

This study investigates an investigational medicinal product (IMP) that is not approved for general use by regulatory authorities such as the European Medicines Agency or the U.S. Food and Drug Administration, but has been authorised for use within this clinical trial.

URBAGEN was developed by the CTNNB1 Foundation and the Gene Therapy Research Institute. Construct design and initial preclinical testing were performed at the Children’s Medical Research Institute in Sydney, Australia.

Full trial details are available here:
https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-522719-40-00

https://clinicaltrials.gov/study/NCT07270549

Why We Are Fundraising

The GAIN-CTNNB1 clinical trial is active and ongoing. To continue enrolling and treating additional children, and to conduct the study in compliance with medical and regulatory requirements, funding is required to cover clinical trial costs.

Developing a gene therapy typically requires €150-250 million when led by a pharmaceutical company. Through nonprofit development, volunteer scientific work, and extensive fundraising, URBAGEN has reached clinical testing with a total development cost of approximately €5 million.

The clinical trial phase is the most resource-intensive stage.

The trial is currently open in Slovenia (Europe). In 2026, we plan to expand to additional clinical sites in Spain and the United States, enabling more children to participate.

All funds raised through this campaign will be used directly for the clinical trial, including:

Hospital costs related to treatment and patient care
Clinical trial operations, monitoring, and regulatory activities
A natural history study used as a comparator for clinical outcomes

The availability of funding directly determines how many children can be treated within the trial.

What is CTNNB1 Syndrome?

CTNNB1 syndrome is a rare and severe neurodevelopmental disorder that affects nearly every aspect of a child’s life, impairing movement, communication, and cognitive development, while also causing significant behavioral and sleep challenges. These difficulties extend beyond the individual, profoundly impacting the quality of life of the entire family.

In some children, the progression of spasticity and dystonia has been observed. Although these children may learn to walk in early childhood, this ability can be lost over time due to worsening of symptoms. As these symptoms progress, children may gradually lose previously acquired skills such as walking, self-feeding, and other aspects of independence.

With this treatment, we don’t just hope, but we expect to not only stop the progression of symptoms but also to improve their current development. That’s why it is so urgent for children to receive this therapy as soon as possible.

Who Are We?

The CTNNB1 Foundation is a global, research-driven nonprofit dedicated to developing life changing gene therapies for children with CTNNB1 syndrome.

We collaborate with leading researchers, scientists, clinicians, and institutions around the world to turn hope into real medical breakthroughs.

The clinical trial has begun, but its future depends on continued funding. Every contribution directly supports clinical care, hospital costs, and trial activities.

By supporting this effort, you are helping make it possible for more children to take part in this study.

Fundraise for CTNNB1 Clinical Trial

This is no longer just research. It is happening for our children.

Team Members