For children diagnosed with Sanfilippo syndrome, there is currently no cure and no approved treatment.
A rare form of childhood dementia, the condition progressively damages the brain, taking away a child’s speech, mobility and memories. For families, the diagnosis marks the beginning of a heartbreaking journey filled with uncertainty.
Today, thanks to the generosity of our community and a research fund established in memory of one special child, there is new hope.
Where generosity meets discovery
Established in 2004 by Ms Natalie McConaghy in memory of her nephew, Malcolm Douglas Grant, the Malcolm Douglas Grant Research Fund was created to support research into Morquio syndrome, mucopolysaccharidoses and related genetic disorders, including Sanfilippo syndrome.
Through the Women’s & Children’s Hospital Foundation, the fund supported PhD researcher Dr Zarina Greenberg (pictured above) to investigate an important question: could existing medicines be repurposed to help children living with Sanfilippo syndrome?
Her work has now been published in two papers in Nature, one of the world’s leading scientific journals. The publications place South Australian research on the global stage and provide an important foundation for future treatment development.
An important step forward
The research uncovered important clues about how Sanfilippo syndrome affects the developing brain, helping explain some of the behavioural and cognitive changes experienced by children with the condition.
It also explored whether medicines already approved for other conditions could be repurposed to help children living with Sanfilippo syndrome. Using patient-derived brain cells, advanced imaging and artificial intelligence, the team screened 63 existing medicines and identified nine that significantly improved cell function within two weeks.
Several of the medicines reduced brain cell damage, while others restored critical signalling linked to learning and behaviour. The findings also suggest that combining treatments may produce stronger, longer-lasting effects.
Because these medicines are already approved for other conditions, successful combinations could offer a more direct pathway to clinical trials than entirely new therapies.
For Zarina, the findings represent an important step towards better outcomes for children living with Sanfilippo syndrome.
“We hope these findings will stimulate further research and ultimately translate into treatments for these children.” – Dr Zarina Greenberg
A legacy making a difference
More than 20 years after it was established, the Malcolm Douglas Grant Research Fund continues to make a meaningful impact.
What began as one family’s commitment to honour Malcolm’s memory has helped drive discoveries now being shared with researchers around the world.
There is still important work to be done before this research is ready to move into clinical trials. The next stage will focus on identifying the most effective combinations of medicines, determining appropriate doses and treatment schedules, and ensuring they can be used safely in children.
Through the Women’s & Children’s Hospital Foundation, supporters help make research like this possible, funding discoveries that bring us closer to better outcomes for children and families facing complex childhood diseases.
Citations
Title: Drug screen and machine learning predict neuroprotective agents in a preclinical human model of childhood dementia
Authors: Greenberg, Z., McDonald, E., Noreña Puerta, A., Inushi De Silva, M., Christensen, C., Adams, R., Tran, J., Mazzachi, P., Loskarn, S., Mubarokah, S.N., Winner, L., Neavin, D., Maack, M., Elvidge, K.L., Melton, L., Hutchinson, M.R., Hemsley, K.M., Smith, N. & Bardy, C.
Journal: Nature Communications (2026) in press
Title: Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.
Authors: Mazzachi, P., McDonald, E., Greenberg, Z., Noreña Puerta, A., Tran, J., Inushi De Silva, M., Christensen, C. Adams, R., Loskarn, S., Beard, H., Zabolocki, M., Elmasri, M., Maack, M., Elvidge, K.L., Hutchinson, M.R., O’Neill, C., Hemsley, K.M., Melton, L., Smith, N. & Bardy, C.
Journal: Nature Communications 17, 3161 (2026).
