SUCCEED trial

The SUCCEED (Systematically Understanding and managing Comorbidities in Childhood Epilepsy Encephalopathy Disorders) project aims to find an easier way to examine the effect of drugs on childhood epilepsy, using the eye and ear as more accessible places to measure neuronal electrical response to light and sound, respectively.

Developmental and epileptic encephalopathies (DEEs) occur in one in every 590 births and are the most severe subgroup of epilepsies. A genetic basis for DEE can now be identified in over half of patients, heralding an era of personalised medicine. Most patients have multiple comorbidities, such as abnormalities of sleep, vision, hearing and cardiac function. These are significant issues for patients and their carers, and often impact quality of life more than seizures. Despite this, little is understood about the comorbidities associated with each genetic DEE, with essentially no evidence-based treatment strategies for these comorbidities.

The SUCCEED project involves PhD student Georgina Liapis, supervised by A/Prof Bryony Nayagam (the Department of Audiology and Speech Pathology) and A/Prof Bang Bui (the Department of Optometry and Vision Sciences), as well as involvement Prof Chris Reid (Florey Institute), Dr Katherine Howell (Murdoch Children’s Research Institute) and Prof Pierro Perucca (Melbourne Medical School). The SUCCEED trial has two streams. The first stream will characterise and quantify comorbidities in different genetic DEE, including identifying electrographic signatures for different comorbidities to use as biomarkers to test therapeutic strategies. The second stream will use this knowledge to identify and test precision therapies.

Only three months into her PhD, Georgina, alongside A/Prof Bryony Nayagam and Dr Jackie Ogie, has already collected some data on eyes and ears in a mouse model of Dravet Syndrome. The team’s next step is to measure the same thing but in children with the condition. The team will be using handheld electrophysiology systems to measure visual epileptic responses. A small strip is placed below the eyeline, with a ping-pong sized ball being used to provide illumination, with quick flashes of light eliciting a response on the eye that can be measured through the sensor strip. What’s interesting about this collaboration is that the same measures are being used in both pre-clinical mouse models and human models, the mirror-image tests being capable of detecting very small changes to vision or hearing with the potential to provide a new biomarker for these rare types of epilepsy. This presents an excellent window of opportunity for our team to test various new drugs for rare disease, with opportunities for clinic translation and improve the quality of life for these patients and families.