Aminoglycoside drugs induce efficient read-through of CDKL5 nonsense mutations, slightly restoring its kinase activity.

ABSTRACT: The X-linked CDKL5 gene codes for a kinase whose mutations have been associated with a suite of neurodevelopmental disorders generally characterized by early-onset epileptic encephalopathy and severe intellectual disability. The impact of these mutations on CDKL5 functions and brain development remain mainly unknown, although the importance of maintaining the catalytic activity is generally recognized. Since no cure exists for CDKL5 disorders, the demand for innovative therapies is a real emergency. The recent discovery that CDKL5 is dosage sensitive poses concerns on conventional protein and gene augmentative therapies. Thus, RNA-based therapeutic approaches might be preferred. We studied the efficacy of read-through therapy on CDKL5 premature termination codons (PTCs

SUBMITTER: Fazzari M 

PROVIDER: S-EPMC6779400 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature