People with Sanfilippo commonly experience frequent respiratory infections, which can lead to pneumonia and long hospital stays. Clinicians typically treat respiratory infections in Sanfilippo once the infection has developed, but in some diseases that affect the lungs, people receive preventative therapy.

One example is the oral antibiotic and anti-inflammatory drug azithromycin. Azithromycin is used in the clinic to treat infections like pneumonia. It is also commonly used as a preventative treatment in children and adults who have cystic fibrosis or severe asthma to help prevent or minimise the impact of respiratory infections.

In this project, Dr Emma Parkinson-Lawrence and her team will test if azithromycin shows promise as a preventative treatment for Sanfilippo using a mouse model of Sanfilippo type A.

Previous research by the group, led by Professor Sandra Orgeig and Dr Emma Parkinson-Lawrence, found that the build-up of heparan sulfate in the lungs of a Sanfilippo type A mouse model leads to reduced lung function and likely a reduced immune response in the lungs. These factors may contribute to a greater susceptibility to respiratory infection in Sanfilippo.

In this project, they will challenge the Sanfilippo mice with a fungus that has the potential to cause a chest infection to confirm whether this is the case, and whether a preventative treatment could help.

The team will expose the mouse model to the fungus Aspergillus fumigatus, which is widely present indoors and outdoors and is often associated with inflammatory lung disease. They will evaluate lung function and how the immune system in the Sanfilippo mice responds to the fungal challenge. They will then investigate whether preventative azithromycin use can improve outcomes for the Sanfilippo mice. If it does show promise, a clinical trial would need to be planned to confirm whether preventative azithromycin treatment is beneficial for patients.

The project will be led by Dr Emma Parkinson-Lawrence, with Co-Investigators Dr Neta Shlezinger, Prof Sandra Orgeig, Prof Doug Brooks, Prof Stavros Selemidis, A/Prof Martin Donnelley, and Dr Sheree Bailey, and Associated Investigators Dr Andrew Thai, A/Prof David Parsons, and Dr Jessica Logan.

“Azithromycin is a cheap and widely available drug that doctors commonly prescribe to children and adults with lung conditions, and because of this, it could be quickly repurposed for Sanfilippo patients,” said Katia Moletta, mother and president at Sanfilippo Fighters. “Our children's quality of life is extremely essential, thus we are enthusiastic to be able to work with the Sanfilippo Children's Foundation to sponsor this project.”

“We are excited to co-fund this project with Sanfilippo Fighters,” Dr Lisa Melton, Head of Research at Sanfilippo Children’s Foundation, said. “This project has the potential to produce results that can go on to improve quality of life for people with Sanfilippo and their families. While a Sanfilippo type A mouse model will be used in the study, results could be applied to all subtypes.”

Dr Parkinson-Lawrence has a research-teaching academic position at the University of South Australia (UniSA) and is a senior scientist and project leader in UniSA’s Mechanisms in Cell Biology and Disease research group. She has dedicated her post-doctoral career to research into mucopolysaccharidoses (MPS diseases), which includes Sanfilippo. Her work focuses on understanding the molecular mechanisms of MPS, particularly in the lungs, with the main goal of improving patient outcomes.

Project Summary

• Project title: Repurposing immunomodulatory drugs for the treatment of recurrent lung infections in a pathogen challenged Sanfilippo type A mouse lung model
• Chief investigator: Dr Emma Parkinson-Lawrence
• Amount:$45,440 from Sanfilippo Children’s Foundation and $45,440 from Sanfilippo Fighters (Italy)
• Duration: 1 year
• Location: University of South Australia
• Status: Active
• Start date: February 2024

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