Uploaded March 2026 | Updated September 2026, 1 week ago
This is a joint presentation with the World Autism Organisation
Free certificates of participation are available upon completion of a brief knowledge quiz: autism.org/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.
Prof. Andrew Levy received his BA Summa Cum Laude from Yale University in Molecular Biophysics and Biochemistry in 1982. He received a MSTP scholarship for his MD PHD training (1982-1990) at Johns Hopkins Medical School performing his PHD under Nobel Laureate Daniel Nathans working on the identification of a growth factor now known as Vascular Endothelial Growth Factor. He completed internal medicine residency at Johns Hopkins Hospital (1990-1992) and a cardiovascular fellowship at Brigham and Women’s Hospital at Harvard Medical School (1992-1996). He is a tenured professor at Technion Faculty of Medicine, Technion Israel Institute of Technology in Haifa, Israel. His current focus of research is on developing treatments for IQSEC2 disease – a neurodevelopmental disorder associated with drug-resistant epilepsy, autism, and severe intellectual disability. Founder of IQSEC2 Research and Advocacy Foundation, a volunteer group of parents working towards providing support for parents, increasing awareness of IQSEC2.
This is a joint presentation with the World Autism Organisation
Free certificates of participation are available upon completion of a brief knowledge quiz: autism.org/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.
Prof. Andrew Levy received his BA Summa Cum Laude from Yale University in Molecular Biophysics and Biochemistry in 1982. He received a MSTP scholarship for his MD PHD training (1982-1990) at Johns Hopkins Medical School performing his PHD under Nobel Laureate Daniel Nathans working on the identification of a growth factor now known as Vascular Endothelial Growth Factor. He completed internal medicine residency at Johns Hopkins Hospital (1990-1992) and a cardiovascular fellowship at Brigham and Women’s Hospital at Harvard Medical School (1992-1996). He is a tenured professor at Technion Faculty of Medicine, Technion Israel Institute of Technology in Haifa, Israel. His current focus of research is on developing treatments for IQSEC2 disease – a neurodevelopmental disorder associated with drug-resistant epilepsy, autism, and severe intellectual disability. Founder of IQSEC2 Research and Advocacy Foundation, a volunteer group of parents working towards providing support for parents, increasing awareness of IQSEC2.
