GENE THERAPY FOR NEUROLOGICAL DISEASE
We develop and characterise novel genetic therapies for intractable neurological diseases, using a variety of in vivo and ex vivo experimental techniques.
Gene therapy for epilepsies
Gene therapy holds promise as a treatment for genetic epilepsies but also as a rational replacement for surgical treatment of pharmaco-resistant focal epilepsy. However, current experimental gene therapies rely either on permanent modification of neuronal function, or on exogenous delivery of agonists to achieve on-demand modulation, and do not discriminate between neurons involved in seizures and healthy neighbour neurons. The lab aims to develop and explore new gene therapy approaches for targeting neurons involved in seizure generation.
In vivo CRISPR editing
Dominant-negative mutations produce faulty proteins that act antagonistically to wild type (WT) gene products, thereby decreasing their function. For this reason, classical gene therapy approaches involving exogenous gene delivery are inappropriate, and directly correcting the mutation in the genome represents the best option.
CRISPR technology has developed rapidly and inserting DNA into post-mitotic cells such as neurons is now possible, although replacing endogenous sequences remains a challenge. In the lab we are using cutting-edge tools in order to achieve the complete correction of the mutated gene in vivo.