Gene Therapy for Mutations in the IQSEC2 Gene
The IQSEC2 protein is a guanine nucleotide exchange factor for Arf6. Pathogenic variants in the X-linked IQSEC2 gene are associated with drug-resistant epilepsy, severe intellectual disability, and autism. The vast majority of disease-causing variants introduce premature termination codons in the IQSEC2 gene, resulting in little or no IQSEC2 protein being produced. We sought to determine if an adeno-associated virus (AAV) containing the IQSEC2 gene could rescue abnormal phenotypes in mice in two different Iqsec2 mouse models with premature Iqsec2 termination codons resulting in a knockout of Iqsec2 gene expression and in mice with a A350V Iqsec2 missense mutation. In Iqsec2 knockout mice, the AAV significantly improved growth, corrected behavioral abnormalities, and normalized the seizure threshold. We propose that success in the Iqsec2 knockout mice warrants a proof-of-concept study for gene replacement therapy in boys with IQSEC2 premature termination variants.
About Our Partner
World Autism Organisation
World Autism Organisation (WAO) is an international nonprofit organization established with a mission to improve the quality of life for people with autism and their families worldwide. It is recognized as the first international organization dedicated to autism.
Learn more at https://worldautismorganisation.com/
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