Sanfilippo syndrome affects the whole body, including the lungs and respiratory system. This leads to frequent respiratory infections in people affected by Sanfilippo, and respiratory obstruction can also affect their sleep. These symptoms have a significant impact on the person with Sanfilippo and the whole family.
There are researchers around the world working to understand the impact of Sanfilippo and similar disorders on the respiratory system. They often use animal models or patient samples to see how the build-up of the complex sugar heparan sulfate (HS) affects this part of the body.
In Australia, Professor Sandra Orgeig and Dr Emma Parkinson-Lawrence at the University of South Australia are spearheading this research. They found Sanfilippo affects the structure of the lubricating substance (called surfactant) which lines the lungs. This surfactant typically helps with breathing and protects against infection. In a Sanfilippo type A mouse model, they showed that there was a reduction of molecules in the surfactant that help with immunity, and lung tissue had over 50 times the normal levels of HS.
Researchers in France and Poland have also looked at how HS affects the lungs. By collecting samples from patients with Sanfilippo, Hurler, and Hunter syndromes, they found that high levels of HS in these diseases impact the delicate balance between different proteins in the lungs, leading to imbalances associated with lung disease.
There is further work underway to understand the impacts of Sanfilippo on the respiratory system. Cure Sanfilippo Foundation (USA) is funding a project led by Dr Neta Shlezinger at the Koret School of Veterinary Medicine, Israel, who is exploring fungal infections in Sanfilippo and how microorganisms in the airway can contribute to MPS-associated pneumonia.
In South Australia, Professor Orgeig and Dr Parkinson-Lawrence are expanding on their work with a team of researchers from Australia and around the world. They are looking further into the effects of Sanfilippo on lung surfactant in an Incubator project funded by Sanfilippo Children’s Foundation. This project includes the analysis of lung samples from mice and from patients with Sanfilippo type A, collected when they are under general anaesthesia for other necessary procedures. This project is ongoing, but the team has already found some changes to the populations of immune cells in the lung in the mice that would be likely to impact susceptibility to infection.
Dr Emma Parkinson-Lawrence is also leading a separate Incubator project, co-funded by Sanfilippo Children’s Foundation and Sanfilippo Fighters (Italy), to see if the drug azithromycin shows promise in preventing or minimising the impact of lung infection in a mouse model of Sanfilippo. If it does show promise, results can inform a potential clinical trial to confirm whether preventative azithromycin treatment is beneficial for patients.
Results from these important studies will help to increase the awareness of respiratory symptoms in Sanfilippo and drive further much-needed research. By understanding how Sanfilippo affects the lungs and respiratory system, researchers can identify and test potential therapies. Research can also inform treatments provided by clinical teams to help minimise the impact on the person with Sanfilippo and their family.
The Clinical Consensus Guidelines for Sanfilippo syndrome, currently available in English, Italian, and Portuguese (with more translations to come), has information for clinicians on respiratory management in Sanfilippo.
