Geertjens Lisa, van Voorst Torben W, Bouman Arianne, van Boven Maaike A, Kleefstra Tjitske, Verhage Matthijs, Linkenkaer-Hansen Klaus, Nadif Kasri Nael, Cornelisse L Niels, Bruining Hilgo
Child and Adolescent Psychiatry and Psychosocial Care, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
N=You Neurodevelopmental Precision Center, Amsterdam Neuroscience, Amsterdam Reproduction and Development, Amsterdam UMC, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands.
Genes (Basel). 2022 Feb 21;13(2):390. doi: 10.3390/genes13020390.
Pharmacological options for neurodevelopmental disorders are limited to symptom suppressing agents that do not target underlying pathophysiological mechanisms. Studies on specific genetic disorders causing neurodevelopmental disorders have elucidated pathophysiological mechanisms to develop more rational treatments. Here, we present our concerted multi-level strategy 'BRAINMODEL', focusing on excitation/inhibition ratio homeostasis across different levels of neuroscientific interrogation. The aim is to develop personalized treatment strategies by linking iPSC-based models and novel EEG measurements to patient report outcome measures in individual patients. We focus our strategy on chromatin- and SNAREopathies as examples of severe genetic neurodevelopmental disorders with an unmet need for rational interventions.
神经发育障碍的药物治疗选择仅限于那些不针对潜在病理生理机制的症状抑制药物。对导致神经发育障碍的特定遗传疾病的研究已经阐明了病理生理机制，以开发更合理的治疗方法。在此，我们提出了我们的协同多层次策略“BRAINMODEL”，重点关注不同神经科学研究层面的兴奋/抑制比例平衡。目的是通过将基于诱导多能干细胞的模型和新颖的脑电图测量与个体患者的报告结局指标相联系，来制定个性化的治疗策略。我们将策略重点放在染色质病和SNARE病上，以此作为严重遗传性神经发育障碍的例子，这些疾病对合理干预存在未满足的需求。
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