Project: Modelling syndromic autism caused by mutations in the ADNP gene

Duration 01/06/2016 - 31/05/2019
Project Topic Autism includes a range of communicative disorders that continues to perplex scientists searching for causes & cures. The project outlined herein provides us with a unique opportunity to study one of the most frequent monogenic forms of autism. Among the many hundreds of genes linked to autism, only a few have been clearly characterized. Last year, we discovered that ADNP is one of a still very limited number of genes that lead to autism in a substantial proportion of cases. ADNP shows recurrent de novo mutations in autism individuals. The gene encodes a neuroprotective protein, ADNP, that is involved in chromatin remodelling and additional cellular functions. It has been demonstrated that many of its protein functions can be replaced by a single octapeptide NAP that is being developed as a drug under the name davunetide. In this multi-disciplinary project, we will accurately define the abnormities associated with the disorder in patients and model the disorder in mice. In parallel with tests to monitor the effect of NAP on animal performance, additional circuits in disease-relevant pathways will be identified through analysis of induced pluripotent stem cells and their differentiated derivatives. We will also elucidate the mutation mechanism of the most frequent ADNP mutation itself, since in order to prevent or treat the disease it is imperative to understand the molecular details of the intergenerational and somatic instability leading to the observed recurrent mutations.
Call Neurodevelopmental Disorders

Project partner

Number Name Role Country
1 Universteit Antwerpen Coordinator Belgium
2 Tel Aviv University Partner Israel
3 IEO - Istituto Europeo di Oncologia Partner Italy
4 The Hospital for Sick Children Partner Canada