CDKL5 disorder is a rare, severe neurodevelopmental disorder that mostly affects girls. CDKL5 patients show a range of phenotypes including seizures that begin in the first few months of life, visual impairment, gastrointestinal difficulties, mental retardation and autism. They are unable to walk, talk or feed themselves. To date approximately 400 individuals with a CDKL5 mutation have been described worldwide. However, given the lack of knowledge regarding the pathophysiology and natural history of the CDKL5 disorder, cases with CDKL5 mutations may have been missed. Currently, there is no cure or effective treatment for CDKL5 disorder, and the mainstay of care for this disorder is support for the families. Therefore, identification of therapies for CDKL5 disorder will represent an important social challenge.
The goal of this project is to identify therapies for CDKL5 disorder, taking advantage of the consolidated expertise of the research group, which are actively involved in different fields of neurosciences. Precisely, we aim to develop and evaluate the efficacy of therapeutic approaches targeting molecules affected by CDKL5 mutations, both in a Cdkl5 mutated mouse model and patient-derived cells. Treatment options will range from pharmacological drug therapies to an innovative “protein substitution therapy" that compensates for the lack of function of the mutated gene. We have extremely promising preliminary results, suggesting that a CDKL5 protein therapy could be indeed an effective therapeutic approach. Altogether, we deem that the approaches used in this project shall ensure achievement of substantial advances in the development of new interventions for this disorder.