Gene Therapy for Fragile X
AAV based gene therapy of Fragile X Syndrome.
Fragile X Syndrome (FXS) is the most common single-gene form of autism spectrum disorder and intellectual disability, with no treatment or cure available. Researchers have developed a therapy that focuses on restoration of FMRP expression through AAV transfection to correct FXS pathology, including abnormal EEG and autistic-like behavior. A novel AAV vector informed by contemporaneous clinical trials of loss of function CNS diseases has been designed. An AAV-mediated approach is advantageous due to extensive use in FDA-sanctioned clinical gene therapy trials (60+), including approval of voretigene neparvovec; vectors transduce post-mitotic neurons/glia expressing only the protein of interest and remain in transfected areas; AAV is capable of long-term gene expression, eliminating the need for multiple treatments; and AAV is non-integrating into host DNA (classified as such by EMEA and FDA), which decreases risk of severe adverse effects. The human FXS program is distinguished by the development of translational quantitative EEG biomarkers of disease severity and treatment response. A biomarker of cortical hyperexcitability has been identified and can be utilized for patient selection and monitoring.
Treatment of impairments associated with FXS: cognitive disability, communication and social skill deficits, sensory sensitivity, inattention, adaptive behavior deficits, anxiety, autonomic system dysregulation, and seizures.
- Novel AAV approach
- Validated EEG biomarker based patient monitoring
- Monogenic disorder
Fragile X Syndrome is a rare disease affecting 1:3000 males and 1:7000 females, with fewer than 200K cases per year in the US. No treatment or cure are currently available.
Ernest Pedapati, MD; Craig Erickson, MD; Christina Gross, PhD; John Sweeney, PhD; Michael Hong