Targeting the immune system as a treatment approach for Sanfilippo

The Sanfilippo Children’s Foundation has awarded funds to Associate Professor Kim Hemsley (Flinders University) and Dr. Marten Snel (South Australian Health and Medical Research Institute). The two-year translational project will evaluate if drugs that target the immune system could benefit children with Sanfilippo.


(Photographer: Tom Huntley)

Breakdown of the complex sugar molecule, heparan sulfate, is impaired in Sanfilippo Syndrome, due to a deficiency in an enzyme required to perform this role. Heparan sulfate builds up inside cells of the body and triggers the immune system, leading to cell damage, especially in the brain.

In this project, Assoc. Prof. Kim Hemsley and Dr. Marten Snel will test compounds that target a part of the immune system on a mouse model of Sanfilippo Type A, by intravenous injection into the bloodstream, or via direct injection into the cerebrospinal fluid.

The team will determine how effective the therapies are in preventing cell degeneration and cognitive decline. If a therapy is proven to be successful, this research will provide a new avenue for exploration in the treatment of Sanfilippo.

Megan Donnell, Executive Director of the Sanfilippo Children’s Foundation, said: “This project will help to develop a greater understanding of the role of the immune system in Sanfilippo and identify potential therapeutic avenues. By limiting the level of inflammation in the brain, it may be possible to slow down the cognitive decline experienced by children with Sanfilippo and improve their quality of life.”

Project Update 

Professor Kim Hemsley and Dr Marten Snel were awarded a Translational Research Grant in the 2019 grant round for their project entitled ‘Targeting the immune system as a treatment approach for Sanfilippo’. The project aimed to target parts of the immune system in the brain to see if neurodegeneration in Sanfilippo can be prevented. Their project to study two drugs known to reduce brain inflammation in a mouse model of Sanfilippo type A is now complete. 

For the first drug, the team which includes Dr Adeline Lau, undertook studies to measure its distribution and stability following injection directly into the fluid surrounding the brain. They found the drug remained in the brain for at least 3 days following a single injection. They also found that the drug could remain stable for up to one month in a drug delivery device that continuously infuses the drug into the brain over a longer period, which would eliminate the need for regular invasive injections. Using this drug delivery device, the drug was then administered to the cerebrospinal fluid of mice with Sanfilippo type A from 6 weeks of age until the mice were 5 months old. At 5 months of age, the mice with Sanfilippo that received the drug showed improvements in motor function compared to control sham-treated mice with Sanfilippo, as well as some small potential improvements in locomotor activity levels and a reduction in anxiety. When the team looked at the brain tissue of these mice, they could see that the drug had reduced the number of immune cells in the brain in an inflammatory state, and also reduced other key inflammatory molecules. There were also some small, but not statistically significant, improvements in neuron structure in some parts of the brain.

While they experienced some delays to the planned second half of their project, the team were also able to begin to explore the use of a second, naturally-derived drug known to target a key immune molecule that contributes to neuroinflammation. Initial data collected by the team indicate that the mice with Sanfilippo treated daily with the drug have reduced liver and spleen sizes compared to untreated affected mice. They are continuing to explore whether this drug has any significant effects on the damage and inflammation seen in the brain. As this drug has previously been explored in a clinical trial with adult patients with another condition, its time to the clinic may be reduced if further data support its use in Sanfilippo.

Although their grant has officially concluded, Professor Kim Hemsley, Dr Adeline Lau and Dr Marten Snel continue to study these two anti-inflammatory drugs and other potential drugs that may prevent or reduce neuroinflammation and neurodegeneration in all types of Sanfilippo.

Associate Professor Kim Hemsley is Head of the Childhood Dementia Research Group. She is predominantly interested in the development of the disease process in Sanfilippo Syndrome, and in evaluating therapy effectiveness. As a direct result of her team’s collaborative research, a number of on-going Sanfilippo gene therapy human clinical trials have been initiated.

Dr. Marten Snel is Head of the Proteomics, Metabolomics and MS-Imaging Facility at the SAHMRI. He is an internationally recognised mass spectrometrist, who has extensive collaborations with Sanfilippo researchers Australia wide. He has been heavily involved in Sanfilippo research, particularly in the development of a test for heparan sulfate, which has the potential to be used as a Sanfilippo diagnostic and prognostic tool.


Project Summary

  • Project title: Targeting the immune system as a treatment approach for Sanfilippo
  • Chief investigators: Associate Professor Kim Hemsley and Dr. Marten Snel
  • Amount: $355,000
  • Duration: 3 years (extension granted)
  • Location: Flinders University and the South Australian Health and Medical Research Institute (SAHMRI)
  • Status: Completed
  • Start date: July 2020

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