Exploring gene therapy with the University of Oxford

Lead researchers: Prof Matthew Wood and Dr Thomas Roberts

Partners: University of Oxford | Great Ormond Street Hospital Children’s Charity

Start date: 2021

This research explored a new way to help treat Dravet Syndrome by increasing the amount of SCN1A protein the body makes.

Mutations in the SCN1A gene are linked to 90% of cases of Dravet Syndrome, meaning cells don’t make enough SCN1A protein. SCN1A activity is naturally kept low by small parts of the gene called upstream open reading frames (uORFs). Therefore, this research investigated whether uORFs could be interfered with, to increase SCN1A levels.

The team first tested an ASO approach that had shown promise in earlier studies. However, when they repeated the work, it did not increase protein levels. These results have now been published and suggest that this particular approach is unlikely to be helpful for Dravet Syndrome.

The research team is now looking at other ways to increase SCN1A, including exon skipping and CRISPR-based base editing.

This work is important because treatments that target the underlying cause of Dravet Syndrome could make a real difference to seizures and other aspects of the condition. This research helps us understand which approaches are less likely to work, as well as which ones may be more promising for the future.