Developmental biologist Dr Sarah Withey is using mini liver 'organoids' made from patients’ stem cells to test a potential treatment for children with a rare, genetic, progressive, life-limiting disease – Ataxia Telangiectasia (A-T).

The inherited disease usually causes loss of control of movement, increased susceptibility to a range of cancers, respiratory complications, and fatty liver disease, where the liver is unable to process lipids, including fats.

“Liver disease is otherwise rare in children,” says Sarah, a researcher at the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland.

“It’s a serious condition that can further limit the life of these kids, who are already dealing with the range of other complications of A-T.”

To investigate the mechanisms of the disease in the liver, Sarah has generated the first patient stem cell-derived liver organoids that exhibit the fatty liver disease associated with A-T.

“By looking at these liver organoids grown from A-T patients’ stem cells, we’ve noticed that an enzyme, which is key to fat metabolism, is in the wrong location in the cells. This means the liver cells can’t process fats properly, causing a build-up characteristic of fatty liver disease.”

Sarah’s research is trialling the introduction of a synthetic, gene-edited enzyme into the cells. Hopefully, this will put the enzyme back where it belongs in the organoid cells to restore fat metabolism.

“We’re going to trial a drug candidate that’s shown promise in other species and other human cell types,” she says. “So, I think there’s a good chance that it will work on these liver cells.”

“From here, we would be in a really good position to get the drug into a clinical trial, providing the first treatment option to repair liver disease in kids with A-T.”

Sarah’s research has been selected for the National Stem Cell Foundation of Australia’s 2021 Matched Funding Program to help address fatty-liver disease symptoms of A-T in kids.

As part of the program, the Foundation matches, dollar-for-dollar, donations made by other supporters to provide a total of $100,000.

The Foundation will match the generous gift of $50,000 already pledged from A-T patient support group BrAshA-T to support Sarah’s trial.

“BrAshA-T have such passion for finding a cure for A-T, and we are trying to bring that passion to life through our research,” she says.

“Being selected for the matched funding program is humbling because it shows that the Foundation also cares about this disease and our work. This is especially important for rare diseases such as A-T, which often lack research and funding investment.

“I’d also like to thank the Foundation for supporting this research and giving an early-career researcher an opportunity that might otherwise be afforded to a more senior researcher. This early-career support is a real foot in the door.”