Angelman Syndrome

Angelman syndrome (AS) is a neurodevelopmental condition estimated to affect between 1 in 12,000 and 1 in 24,000 people, both males and females. AS is caused by a deletion or mutation in the ubiquitin protein ligase E3A (UBE3A) gene on chromosome 15.

Characteristics of AS are delayed development, intellectual disability, anxiety and hyperactivity, severe speech impairment, problems with movement and balance, seizures and sleep disorders. AS has often been misdiagnosed as autism. Many symptoms persist into adulthood and people with AS require lifelong care and support from clinicians and caregivers.

NNZ-2591 was tested in the ube3a knockout mouse model, which resembles features of Angelman syndrome in humans and includes motor deficits, learning problems and alterations in synaptic connectivity and plasticity. The study compared normal mice and "knockout mice" with a disrupted gene. In the knockout mice, treatment with NNZ-2591 for 6 weeks normalized the deficits in all the tests of anxiety, daily living, sociability, motor performance and cognition as well as eliminating seizures.

On 9 August 2024, Neuren announced top-line results from a Phase 2 clinical trial of NNZ-2591 in children with AS. Significant improvements were observed in both clinician and caregiver global efficacy measures specifically designed for AS. Improvements were seen in clinically important aspects of AS.

Neuren has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for NNZ-2591 to treat AS.