AI screen finds nine candidates in childhood dementia lab model

Skin cells taken from children with Sanfilippo syndrome were given a new identity in the laboratory. Reprogrammed into brain cells, they reproduced the disease's toxic buildup, inflammation and ongoing cell loss. That gave an Australian research collaboration a human model in which to test treatments without waiting for a new drug to be invented.

The team screened 63 existing medicines using advanced imaging and artificial intelligence. Nine drugs significantly improved cell function within two weeks. Several reduced brain-cell damage; others restored signaling associated with learning and behavior. The study was published in Nature Communications.

The work builds on another finding from the same team: brain cells from children with Sanfilippo become abnormally excited during early development and remain stuck in overdrive. In the new study, the researchers identified a combination of repurposed drugs that returned cell activity toward healthy levels. The proposed mechanism could matter for symptoms such as hyperactivity, while potentially protecting against irreversible neuronal loss if the result translates to patients.

Sanfilippo syndrome is a rare, progressive childhood dementia with no widely available treatments. According to Medical Xpress, it belongs to a group of more than 100 genetic disorders that together affect 1 in 2,900 children in Australia; half of all children with dementia die by age 10. Professor Cedric Bardy, of Flinders University, SAHMRI and Brain Organoid Therapeutics, led the research effort.

So what changes for families now? Not a prescription: these are preclinical results from lab-grown cells, and clinical trials are still needed. But the shortlist could shorten the route to testing because the nine medicines are already approved by Australia's TGA for other conditions. The researchers say such treatments could manage daily symptoms and slow brain damage while gene therapies, which they describe as essential for a cure, continue to be developed.