Children with Sanfilippo lack a functional version of one of the enzymes required to break down the complex sugar molecule, heparan sulfate. As a result, the heparan sulfate builds up inside the body to toxic levels, resulting in the devastating effects of Sanfilippo.

 As most of the symptoms are related to the brain, most research has focused on the neurological aspect of the disease. However, there are other bodily systems impacted by Sanfilippo, and there is little information known about why these symptoms result.

One organ implicated in Sanfilippo is the lungs; children with the condition experience lung infections that result in distressing and long hospital stays, and respiratory complications are the leading cause of death for those suffering from Sanfilippo. It is thought that the excess heparan sulfate may accumulate in the substance lubricating the lungs, which is known as pulmonary surfactant, directly affecting lung and surfactant function as well as the function of the local immune system.

In this study, Prof. Orgeig and Dr. Parkinson-Lawrence will use a Sanfilippo Type A mouse model, along with samples from children with Sanfilippo Type A. Samples of fluid from the lungs of children with Sanfilippo will be collected (with consent) when they are under general anaesthesia for necessary surgery to help manage the condition, for example, tonsillectomy.

 By analysing the surfactant that lubricates the lungs in humans and mice, the project will determine if there is increased heparan sulfate, and whether this reduces the effectiveness of surfactant. Key immune system components involved in fighting infections will also be studied, to examine whether their function is impaired.

The results of this study will provide much-needed information on how the respiratory complications of Sanfilippo could be better managed. “Investigating the mechanism of how Sanfilippo affects the lungs has the potential to result in changes to clinical practice relatively quickly. This could go a long way to improving the quality of life for children with Sanfilippo”, said Megan Donnell, Executive Director of the Sanfilippo Children’s Foundation.

Prof. Sandra Orgeig is a pulmonary biologist, who has received international recognition for her work on the evolution, development and function of pulmonary surfactant. Her current major interest concerns how lungs are affected in lysosomal storage diseases.

Dr. Emma Parkinson-Lawrence is a biochemist who has long been interested in the underlying mechanisms of lysosomal storage diseases, including Sanfilippo Syndrome. She has presented at several international conferences on the topics of MPS and related diseases.

Project Summary 

• Project title: Peripheral pulmonary pathology informing clinical treatment for Sanfilippo patients
• Chief investigators: Prof. Sandra Orgeig and Dr. Emma Parkinson-Lawrence
• Amount: $33,000
• Duration: 3 years (extension granted)
• Location: University of South Australia
• Status: Active
• Start date: April 2020