TOP ＞ Plenary Lecture

Plenary Lecture Neurodevelopmental disorders: From basic mechanisms to clinical trials 2L1 Neurodevelopmental disorders: From basic mechanisms to clinical trials Ype Elgersma ENCORE expertise center for neurodevelopmental disorders; Department of Neuroscience; Erasmus MC University Medical Center, Rotterdam, The Netherlands Intellectual disability (ID) is present in 2% of all children. Recent evidence suggests that in the majority of the cases a genetic mutation is the primary cause of the intellectual disability. Knowledge of the role of mutated gene is an important step in trying to understand the molecular mechanisms leading to ID, and helps us to design therapeutic strategies in which we try to ameliorate the symptoms associated with these disorders. In this presentation I will in particular focus on our research on Angelman Syndrome. Angelman syndrome (AS) is a severe neurological disorder, affecting 1:20,000. Children with AS present with severe intellectual disability, motor dysfunction and absence of speech. In addition, there is a high comorbidity with epilepsy and behavioral deficits. AS is caused by spontaneous mutations in the UBE3A gene. Currently, there are no effective treatments for this devastating disorder. Therefore, the primary aim of our research is to advance our knowledge of the underlying pathophysiology of AS with the ultimate aim to identify promising approaches for improving therapeutic treatment. References:Overwater IE et al.(2016) Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology 87:1011-1018Elgersma Y (2015). Neurodevelopmental disease: A molecular tightrope. Nature 526, 50–51 Bruinsma CF et al. (2015) Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model. J. Clin Invest. 125:4305–4315 Silva-Santos S et al. (2015) Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model J. Clin. Invest. 125:2069-2076 Omrani A et al. (2015) HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1 Mol. Psych. 20, 1311-1321Goorden SMI et al. (2015) Intact neuronal function in Rheb1 mutant mice: implications for TORC1 based treatments Hum. Mol. Gen. 24:3390-8 Van Der Vaart T et al. (2015) Treatment of cognitive deficits in genetic disorders: a systematic review of clinical trials JAMA Neurol. 72:1052-1060Abs E et al. (2013) TORC1-dependent epilepsy caused by acute biallelic Tsc1 deletion in adult mice. Ann Neurol 74:569–579 Van Der Vaart T et al. (2013) Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet Neurol 12:1076–1083