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July 01-02, 2019 | Paris, France
Brain Disorders and Therapeutics
6th International Conference on
Journal of Brain and Neurology | Volume: 03
Pharmacotherapy with Sertraline improves Brain development and Behavior in a
mouse model of CDKL5 Deficiency Disorder
Elisabetta Ciani, Claudia Fuchs, Laura Gennaccaro, Stefania Trazzi and Giuseppe Galvani
University of Bologna, Italy
CDKL5 deficiency disorder (CDD) is a rare
neurodevelopmental disease caused by de novo
mutations in the X-linked CDKL5 gene. The consequent
misexpression of the CDKL5 protein in the nervous system
leads to a severe phenotype characterized by intellectual
disability, motor impairment, visual deficits and early-
onset epilepsy. No therapy is available for this devastating
disorder. Recent studies have implicated alterations
in serotonin (5-HT) signaling in neurodevelopmental
disorders (NDDs), such as autism spectrum disorders, RTT
and Down syndrome, suggesting that drugs targeting the
5-HT system might be a valid treatment option for NDDs.
Interestingly, we found a deregulation of the 5-HT2A
receptor expression, an important player in cognitive
processes, in the hippocampus and cortex of an animal
model of CDD, the Cdkl5 knockout (KO) mouse, suggesting
a Cdkl5-dependent dysregulation of the 5-HT system.
Importantly we found that treatment with Sertraline, a
selective serotonin reuptake inhibitor, improved brain
development and behavior in Cdkl5 KO mice. Our result
might represent a fundamental pre-clinical step with a high
translational impact for the amelioration of CDKL5-related
symptoms.
Speaker Biography
Elisabetta Ciani, PhD, Neurophysiologist. Professor of Physiology at
the Medical School of the University of Bologna. Trained in genetic,
molecular and cellular biology during her postdoc at the Max Planck
Institute, Munich (1995-1999). Dr. Ciani is an expert in dendrite and
synapse development in the Central Nervous System. In particular,
she studies development of dendritic spines and neuronal maturation
in various models of neurodevelopmental disorders including Down
syndrome and CDKL5 disorder. Her group has collaborated to develop
a first mice model of the CDKL5 disorder. She has developed a protein
therapy for CDKL5 disorder (inventor, Patent WO2015128746A3). She
has 76 publications, and her publication H-index is 35.
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