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.
Neuren has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) for NNZ-2591 to treat AS. The required manufacturing development and non-clinical toxicity studies are progressing in preparation for clinical trials in 2020.