Grant Award Details

AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder
Grant Number: 
DISC2-13417
Project Objective: 
  • To develop and show disease modifying activity for a CRISPR-based epigenome editing approach to reactivate the healthy copy of CDKL5 from the inactive X chromosome in females with CDKL5 Deficiency Disorder.
Investigator: 
Name: 
Type: 
PI
Disease Focus: 
Epilepsy
Neurological Disorders
Other
Human Stem Cell Use: 
iPS Cell
Award Value: 
$1,429,378
Status: 
Pre-Active

Grant Application Details

Application Title: 
  • AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder
Public Abstract: 

Research Objective

We propose a gene therapy for the treatment of a severe infantile epilepsy called CDKL5 Deficiency Disorder using CRISPR-mediated epigenetic editing

Impact

A transformative treatment for females affected by CDKL5 Deficiency Disorder in addition a platform for the approximately 38 other X-linked intellectual disabilities that predominately affect females

Major Proposed Activities

  • Validation of CRISPRe in CDD human neuronal cell models
  • Safety and Off-Target profile of CRISPRe in CDD human neuronal cell models
  • Rescue of behavioral and functional outcome measures in two mouse models of CDD following CRISPRe administration
  • Molecular and Histological Characterization following CRISPRe administration in two mouse models of CDD
  • Safety of CRISPRe in two mouse models of CDD
Statement of Benefit to California: 

CDKL5 Deficiency Disorder (CDD) occurs in 1 of 40,000 live births meaning there are ten CDD patients born in California each year. CDD has a drastic impact on the quality of life for both the patient and caregiver. Over 43,000 people in California have an intellectual disability. A high number of causative genes for intellectual disabilities are found on the X chromosome. This grant will not only develop a treatment for CDD but may provide a roadmap to treat other X linked disorders.