Fast-tracking childhood epilepsy treatments

Affecting around 1% of the population, epilepsy is the most common neurological condition in Australia. This includes one in 2000 babies born with severe childhood epilepsy – babies who live with recurrent seizures and who do not reach developmental milestones as the result of mutations in just a single gene. Investigating these genetic changes is The Florey’s Associate Professor Snezana Maljevic – her team’s goal is to develop new disease models to find effective treatments for the condition.

At the core of their work is a partnership with US biopharmaceutical company Praxis, co-founded by Florey colleague and fellow epilepsy researcher Professor Steven Petrou. To better understand how the disease behaves in childhood genetic epilepsy, the team has been investigating pre-clinical mouse and patient-derived stem cell models. Of particular interest are brain ‘organoid’ models that can replicate neurodevelopmental processes.

These models have the potential to offer valuable insights into how single gene mutations lead to seizures and the effects they have on the brains of children and their development in very early in life.

Associate Professor Maljevic said that by using these models they can see how potential treatments may or may not work. One of the treatments currently being investigated at The Florey is antisense oligonucleotide therapies.

“These therapies use small, singlestranded synthetic pieces of DNA that can specifically bind to mRNA, which encodes the gene of interest, to either block its ability to make a protein or influence the amount of protein produced in other ways,” explained Associate Professor Maljevic.

“They can be effective therapy for genetic epilepsy as they can normalise the amount of protein produced by a gene carrying an epilepsy causing mutation.”

Associate Professor Maljevic said that the partnership with Praxis has enabled her team to undertake an amount of work that would normally require several years, in just the last year alone.

“It is fantastic to see the excitement of everyone on the team as we have a real opportunity to positively impact lives of children living with epilepsy.”