Huda Zoghbi, MD, Baylor College of Medicine, Houston, TX, discusses possible therapy strategies for Rett syndrome and MECP2 duplication disorders. In the case of Rett syndrome, one potential strategy is gene therapy to deliver a non-mutated version of the MECP2 gene, enabling the production of a healthy form of the MeCP2 protein. However, it is crucial to be mindful that approximately 50% of the cells are already expressing normal protein levels and ensure acceptable levels of MeCP2 expression to avoid overexpression and cause duplication syndromes. Another possible strategy for Rett syndrome is early pre-symptomatic intensive training to improve functionality and behavior. In animal models, pre-symptomatic training was able to delay the disease course by 5 months, highlighting the importance of early diagnosis to have a chance to train the infants and delay the course of Rett syndrome. For MECP2 duplication syndrome, approaches to normalize the MeCP2 protein levels are being developed, including antisense-oligonucleotides that have been studied in animal models and are now paving the way for clinical trials. This interview took place during the European Academy of Neurology 2021 congress.
Dr Zoghbi collaborates with Ionis Pharmaceuticals on ASO therapy for MEDCP2 duplication syndrome.