Pitt Hopkins syndrome (PTHS) is a neurodevelopmental condition affecting both males and females, caused by the loss of one copy or a mutation of the TCF4 gene on chromosome 18. The incidence of PTHS is not known, however it has been estimated as between 1 in 11,000 and 1 in 41,000 people.
Characteristics of PTHS are developmental delay with moderate-to-severe intellectual disability and behavioral differences, hyperventilation and/or breath-holding while awake, seizures, gastrointestinal issues, lack of speech, sleep disturbance, stereotypic hand movements and distinctive facial features. Some individuals with PTHS are diagnosed with autism.
NNZ-2591 was tested in the tcf4 mutation mouse model, which exhibits features of PTHS in humans, comparing normal mice and mice with a disrupted tcf4 gene. In the mice with a disrupted gene, treatment with NNZ-2591 for 6 weeks normalized the deficits in all the tests of hyperactivity, daily living, learning and memory, sociability, motor performance and stereotypy.
Neuren has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) for NNZ-2591 to treat PTHS. The required manufacturing development and non-clinical toxicity studies are progressing in preparation for clinical trials in 2020.