The research activity is aimed at investigating the molecular and cellular mechanisms underlying CDKL5 Deficiency Disorder (CDD), a severe X-linked developmental encephalopathy that predominantly affects females. Mutations in the CDKL5 gene result in reduced or absent functionality of the CDKL5 protein, a kinase that is crucial for the proper development and maintenance of central nervous system functions. Clinically, CDD is characterized by early-onset epilepsy, severe intellectual disability, autism spectrum disorders, motor and visual impairments, and gastrointestinal complications. Currently, no curative therapies are available, making the development of targeted therapeutic strategies a priority.
The main objective of the research is the identification and validation of innovative approaches aimed at restoring CDKL5 protein function and correcting the brain developmental alterations associated with the disorder. To this end, preclinical models are employed, including murine models and patient-derived cellular systems, to evaluate the efficacy and safety of different therapeutic strategies.
Among the approaches under investigation are gene therapy, based on the delivery of coding sequences for functional and secretable forms of the CDKL5 protein, and protein replacement therapy, which involves the systemic administration of recombinant proteins capable of reaching the central nervous system. In parallel, pharmacological strategies targeting the modulation of signaling pathways altered downstream of CDKL5 loss of function are also being explored.
Overall, these studies are aimed at generating robust preclinical evidence to support the future clinical translation of therapeutic interventions for the treatment of CDD.
