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ePoster
GENE THERAPY FOR FOCAL CORTICAL DYSPLASIA TYPE II
Amanda Almacellasand 7 co-authors
UCL
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS02-07PM-351
Presentation
Date TBA
Board: PS02-07PM-351
Event Information
Poster Board
PS02-07PM-351
Poster
View posterAbstract
Focal Cortical Dysplasia II (FCDII) is characterised by malformation of cortical development, frequently associated with drug-resistant epilepsy in children. It is typically caused by somatic mutations resulting in mammalian-Target-Of-Rapamycin-Complex-1 (mTORC1) hyperactivation. Epilepsy surgery is not always effective and is often precluded by proximity to eloquent brain regions, and drug treatment with rapamycin, mTORC1 inhibitor, has severe side effects. Gene therapy is thus currently the most promising option for FCDII.
Recently we have shown that a gene therapy approach aiming to decrease neuronal excitability (symptoms) was effective in decreasing seizures when injected in the FCDII focus of a translational mouse model, but not co-morbidities.
Here, we tested a novel gene therapy approach based on AAV9 expression of an shRNA targeting Rptor, a mTORC1 complex activator, to achieve a more localised and controlled inhibition of mTORC1 signalling. Continuous EEG recordings from adult FCDII mice before and after local AAV9-Rptor-shRNA injection, showed an 82% decrease in seizures (n=10 mice/group). Rescue of co-morbidities and therapeutic window still need to be tested.
This is a novel gene therapy for FCDII that can be expanded to all other mTORopathies with a great potential for translation to the clinic in the next 5 years.
Recently we have shown that a gene therapy approach aiming to decrease neuronal excitability (symptoms) was effective in decreasing seizures when injected in the FCDII focus of a translational mouse model, but not co-morbidities.
Here, we tested a novel gene therapy approach based on AAV9 expression of an shRNA targeting Rptor, a mTORC1 complex activator, to achieve a more localised and controlled inhibition of mTORC1 signalling. Continuous EEG recordings from adult FCDII mice before and after local AAV9-Rptor-shRNA injection, showed an 82% decrease in seizures (n=10 mice/group). Rescue of co-morbidities and therapeutic window still need to be tested.
This is a novel gene therapy for FCDII that can be expanded to all other mTORopathies with a great potential for translation to the clinic in the next 5 years.
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