Australian researchers identify existing drugs to slow rare childhood dementia

Australian researchers have identified nine existing medicines that could slow the progression of brain damage in children with Sanfilippo syndrome, a rare and devastating form of childhood dementia. The discovery, published in Nature Communications, offers a potential shortcut to treatment by repurposing drugs already approved for other conditions—a path that could bring help to families years faster than developing entirely new therapies.

Sanfilippo syndrome is one of more than a hundred genetic disorders that collectively affect roughly one in 2,900 Australian children. The disease strips away memory, behavior, and physical function progressively. Half of the children diagnosed with it do not survive past age ten. Until now, there has been no widely available treatment.

The research team, led by Professor Cedric Bardy at Flinders University's Laboratory for Human Neurophysiology and Genetics, took skin cells from affected children and reprogrammed them into brain cells in the laboratory. These cells reproduced the hallmarks of the disease: toxic buildup, inflammation, and ongoing cell death. Using this platform, the researchers screened 63 already-approved medicines and found that nine of them significantly restored brain cell health within two weeks. Some reduced damage directly; others restored the cellular signaling that underpins learning and behavior. The team also found evidence that combining certain drugs might produce stronger and longer-lasting effects.

What makes this discovery particularly significant is the speed at which it could reach patients. Because these medicines have already been approved by the Therapeutic Goods Administration for other conditions, they can move into clinical trials far more quickly than drugs developed from scratch. The research was supported by funding from the Medical Research Future Fund and coordinated by Megan Maack, CEO and founder of the Childhood Dementia Initiative, who previously led the Sanfilippo Children's Foundation.

In earlier work published in the same journal, the same team had demonstrated that brain cells from children with Sanfilippo become abnormally overactive during early development and remain stuck in that state. The newly identified drug combinations can return these cells to normal activity levels. This matters because it could help children manage symptoms like hyperactivity while also protecting them from irreversible nerve cell loss.

Bardy emphasizes that while gene therapies will ultimately be needed to cure the disease, the immediate need is to manage symptoms and slow damage while those cures are being developed. "By combining human brain cell models with machine learning, we can quickly identify therapies that shift diseased cells toward a healthier state," he said. The research also provides a platform for testing treatments for other brain disorders, including Alzheimer's disease.

The collaboration involved Flinders University, SAHMRI, the University of Adelaide, Women's and Children's Hospital, and several advocacy organizations. Maack noted that the findings matter not just for Sanfilippo but for the entire field of childhood dementia. "What's needed now is sustained and coordinated research funding across the pipeline to accelerate progress for all conditions that cause childhood dementia," she said. The work represents a significant step toward faster, more practical treatments for children facing conditions that have long had no targeted options.