Sanfilippo syndrome is a form of childhood dementia with no current treatment or cure. Often, patients with Sanfilippo and their families encounter significant diagnostic odysseys and further uncertainty regarding disease prognosis. Clinical trials for treatments for Sanfilippo are also hampered by limited ways to track disease progression and responses to treatment. While patient diagnosis, predicting disease outlook, and treatment development are dependent on many factors, one essential tool required for all of these is a collection of accurate biomarkers.

Biomarkers are key indicators that specify the presence, absence, or severity of a disease. They can be the activity of genes in the tissues of the body, proteins or other molecules found in blood or urine, and even features seen on MRI scans.  

While good progress has been made in clinical trials with the tools and biomarkers currently available, faster progress and better informed clinical care could be made possible with new, accurate biomarkers for Sanfilippo.

This project, which involves a multi-disciplinary team of Australian researchers, aims to discover and validate new biomarkers for Sanfilippo to fast-track biomarker translation into the clinic. The team includes A/Prof Jan Kaslin (Australian Regenerative Medicine Institute, Monash University), Dr Louise O’Keefe (The University of Adelaide), Dr Nicholas Smith (The University of Adelaide and Women’s and Children’s Hospital, Adelaide), and Prof Kim Hemsley (Flinders University).

The researchers will collect and analyse patient blood samples and samples from animal and cell models to identify potential biomarkers. With consent, blood samples will be collected from Sanfilippo type A patients, their relatives, and healthy control individuals. Human Sanfilippo cell models, and mouse, zebrafish and fruit fly models of Sanfilippo will also be used. Differences between Sanfilippo and non-Sanfilippo samples, like changes in gene activation or changes in protein levels, will be examined to identify a panel of potential biomarker candidates. 

When candidates are identified, the function of the molecules and their potential as biomarkers will be validated in fruit fly and zebrafish Sanfilippo models previously established by Dr O’Keefe and A/Prof Kaslin, respectively. Validation will involve the removal and reintroduction of the candidate biomarker genes. This process will inform the researchers of the function and impact of the genes on Sanfilippo and disease progression. Importantly, examining the changes in these molecules in the human blood samples will help to confirm whether the biomarkers are suitable for use in the clinic.

Dr Lisa Melton, Head of Research at  the Sanfilippo Children’s Foundation, said: “Through using several different animal models as well as human samples, this project has great potential to identify strong biomarker candidates for Sanfilippo. A set of accurate biomarkers will have a lasting impact on Sanfilippo therapy development and clinical practice, and will ultimately lead to greater treatment outcomes.”

Sanfilippo Children’s Foundation’s contribution to this project has been made possible by a generous Impact Philanthropy grant via Perpetual Trustees.

Associate Professor Jan Kaslin is a group leader at the Australian Regenerative Medicine Institute, Monash University, and created the world’s first Sanfilippo zebrafish model. His research work aims to understand the processes involved in central nervous system damage and how to repair it. 

Project Summary

• Project title: Discovery and validation of translational biomarkers for Sanfilippo childhood dementia
• Chief investigators: A/Prof. Jan Kaslin with Dr Nicholas Smith, Dr Louise O’Keefe & Prof. Kim Hemsley 
• Amount: $157,850 from Sanfilippo Children’s Foundation (with support from Perpetual Trustees), $207,000 from Cure Sanfilippo Foundation (USA), and $50,000 from Fundacja Sanfilippo (Poland).
• Duration: 3 years
• Location: Monash University, The University of Adelaide and The Women’s and Children’s Hospital, Adelaide
• Status: Active
• Start date: July 2022

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