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Headlines 11 Remarkably, as part of the study, Lynette identified the gene mutation that caused his epilepsy, enabling a diagnosis of Developmental and Epileptic Encephalopathy (DEE) – 16 years after he was born. “We'd gone through most of his life with no answers, and were finally able to give a name to his disease and know what caused it,” Caroline says. “It was huge.” Since then, Caroline has picked up this knowledge and run with it. Today, she leads her second Neurological Foundation funded-project to identify further DEE gene variants in a population of tadpoles. It uses medical breakthrough technology such as the CRISPR gene editing tool, and software backed by big data. “We've come to an interesting point in science where we can identify gene mutations in children with epilepsy, but we have absolutely no idea how they derail brain development. And that’s where developmental biologists can jump in and help. That’s only been possible for the last five or six years.” Despite advancements in clinical genetics, Caroline emphasises the lack of tangible solutions for parents facing similar challenges. "We're drowning in data, but offering little hope.” Seizures in infancy are extremely distressing for children and their families and can leave children profoundly disabled. “While current treatments manage the symptoms as best as possible, most children still have daily seizures because we are only treating symptoms and not addressing the cause,” says Caroline. “There are 110 genes now linked to the disease and each child can have a unique mutation within that. In many cases only a handful of patients worldwide will have a specific gene mutation. These conditions, while devastating for families, are so rare individually that they are not of interest to drug companies, and developing targeted treatments will only help a small number of children.” Caroline describes her project as seeking “order from chaos”, as she hunts for commonalities across DEE gene mutations. This sets up a base to test treatments that target multiple types of DEE rather than a single mutation. “Firstly, we need that basic knowledge that confirms a gene variant causes seizures, then we can use that information as a platform to test gene-editing therapies or repurposed drugs.” The project has received two Neurological Foundation grants totalling $460,963 – and is delivering results, thanks to collaboration with fellow Zoology Neuroscientists Drs Bart Geurten and Paul Szyszka and Postdoctoral Fellow Dr Sulagna Banerjee. The team has successfully replicated DEE caused by mutations in the gene NeuroD2 in one-week-old tadpoles. Results suggest the blood-pressure drug losartan reduces seizures caused by this variant. The team is working on other genes as well as developing a machine learning process for detecting seizures. “It is early days, but the work is looking promising,” says Caroline. Caroline's work is generously supported by the Estate of Robin MacDonald Smith, and Epilepsy Foundation of NZ. to neurology Dr Caroline Beck (far left) and her team (left to right) Dr Sulagna Banerjee, Alex Matthews, Dr Paul Szyszka, and Dr Bart Guerten