CRISPR Base Editing for CDKL5 Deficiency Disorder
A multinational consortium spanning Boston, Berlin, and Seoul reports preclinical success using adenine base editors (ABE) to correct CDKL5 pathogenic variants associated with severe early-onset epileptic encephalopathy.
Study Design Notes
Investigators deployed ABE8e editors packaged in engineered AAV9 vectors. Preclinical tests utilized patient-derived cortical neurons and CDKL5 knockout mice.
- • Editing efficiency reached 62% with minimal off-targets.
- • Restoration of dendritic arborization and synaptic density.
- • Seizure frequency reduced by 48% in treated murine models.
Consortium Sites
- Boston Children's Hospital Gene Therapy Program
- Max Delbrück Center for Molecular Medicine, Berlin
- Seoul National University Neurology Lab
Ethical review boards approved cross-border data sharing frameworks with parental consent.
Regulatory & Access Outlook
The consortium prepares for a phase 1/2 clinical trial targeting infants and toddlers with refractory seizures. Orphan drug designation granted by EMA and FDA accelerates regulatory pathways.
Trial Readiness
GMP-grade vector production established in Dublin. Safety toxicology studies ongoing in non-human primates.
Equity Considerations
Access fund proposed to subsidize participation for families from resource-limited regions, incorporating travel support and genetic counseling translations.
Data & Monitoring
Longitudinal monitoring includes EEG biomarkers, neurodevelopmental scales, and immune profiling. A decentralized data platform ensures secure patient-reported outcomes submission.
- • Open science commitment with de-identified datasets released annually.
- • Independent Data Monitoring Committee (IDMC) chaired by Prof. Hana Li.
- • Community advisory board with caregiver representation from four continents.