Bordeaux Neurocampus, Université de Bordeaux, France
Novel therapeutic strategies for neurodevelopmental disorders: lessons from behavioural studies on genetic mouse models
Converging lines of evidence have highlighted the relevance of identifying common etiopathological pathways potentially involved in multiple neurodevelopmental disorders (NDDs). The concept of “channelopathies” has been suggested to include several NDDs of different genetic origins, underlying the role of ionic channels as common therapeutic targets with multiple potential applications. Among them, large-conductance Calcium-dependent potassium (BKCa) channels have received increasing attention, since they play a crucial role in neuronal excitability, neurotransmitter release and synaptic functions. Reduced expression/functionality of these channels has been described in several NDDs, including Fragile X syndrome (FXS), autism spectrum disorder (ASD) and Williams-Beuren syndrome (WBS), so that molecules activating these channels have been proposed as promising treatments for these pathologies. Here we present evidence obtained from genetic mouse models of these NDDs (e.g., the Fmr1-KO and CD mouse lines) providing an extensive neurobehavioral characterization of the therapeutic impact of BKCa agonists, within a drug repurposing setting. Our results clearly demonstrate the marked efficacy of BKCa activators in treating the brain and behavioral abnormalities of our mutant mice, thus encouraging the use of these molecules for clinical applications in the field of NDDs.
Susanna Pietropaolo has carried out her initial studies in behavioural neurobiology at the Italian National Institute of health (ISS), in Rome. She has then obtained her PhD at the ETH of Zurich after 5 years of extensive training in the behavioural validation of mouse models of neuropsychiatric disorders. She worked afterwards as a post-doctoral fellow at the Institute of cognitive and integrative neuroscience (INCIA) at the University of Bordeaux where she became assistant professor (CNRS researcher) in 2012. Since then, she has carried out research on genetic mouse models of developmental disorders, with a special emphasis on Fragile X syndrome and Williams’ Beuren syndrome. Her current research projects have received funding by the Fondation pour l’audition and the Association Autour De Williams.