Therapeutic inhibition of a key inflammation pathway

The Sanfilippo Children’s Foundation has awarded funds to Dr Nicholas Smith at The University of Adelaide and the Women’s and Children’s Hospital in Adelaide. Dr Smith and his collaborators will investigate an important inflammatory pathway and its potential as a therapeutic target for Sanfilippo.

In March 2020, the Sanfilippo Children’s Foundation held the inaugural Solving Sanfilippo Symposium in Adelaide. The event brought together over 30 Sanfilippo researchers from around the country to discuss the current state of Sanfilippo research and needs for the future. Part of the Symposium involved a ‘Sanfilippo Challenge’ - to develop an innovative, collaborative project idea, with the winning project to receive funding from the Foundation. The Foundation received a number of top-quality research proposals, and Dr Nicholas Smith’s project was selected by an assigned scientific review panel.

In this Sanfilippo Challenge grant, Dr Smith and his collaborators from Adelaide and Sydney will investigate a key signalling pathway involved in inflammation, which may exacerbate the progression and symptoms of Sanfilippo. Inflammation in the brain has been implicated in the disease, and anti-inflammatory therapeutic options are being actively investigated. This includes one drug called Anakinra, currently in a clinical trial for Sanfilippo, which targets one of the molecules involved in inflammation in the brain.

The team, which includes internationally recognised immunologists, neuroscientists and biochemists, will investigate another part of the inflammatory pathway using both a Sanfilippo mouse model and globally-sourced samples from patients with Sanfilippo type A. They will suppress the inflammatory pathway in Sanfilippo type A mice and monitor different genes and inflammatory molecules in the brain, as well as the structure of brain cells.

In addition to their laboratory studies, DNA samples will be requested worldwide from patients with Sanfilippo type A. These will be used to investigate an important gene involved in inflammation and determine whether slight changes in this gene are associated with different disease severities. This is significant as patients within subtypes often present with a wide variation in symptoms, and it is not known why this is the case. If changes in this gene are shown to affect disease severity, it will allow the identification of patients whose disease progresses faster because they are more susceptible to this type of brain inflammation. These children might also benefit the most from a therapy that targets this pathway.

“The combination of clinical and scientific experts involved in this project will help to shine a light on major questions in Sanfilippo research today: defining the role that inflammation plays in Sanfilippo, as well as potential reasons for clinical variation between patients,” said Megan Donnell, Founder and Director of the Sanfilippo Children’s Foundation.

Victoria Bowring, CEO of the Foundation, said: “We are proud to fund this research to come out of the first Sanfilippo Challenge event. As a result of this project, key inflammatory steps may be identified as therapeutic targets, potentially adding to the list of therapeutic avenues for Sanfilippo.”

Dr Nicholas Smith is Head of the Neurology and Clinical Neurophysiology Service at Adelaide’s Women’s and Children’s Hospital with a research laboratory at The University of Adelaide. He has significant clinical experience in the Sanfilippo sphere and has been involved in pre-clinical therapy development and clinical trials for Sanfilippo. 

Project Summary

  • Project title: Therapeutic inhibition of a key inflammation pathway
  • Chief investigator: Dr Nicholas Smith
  • Amount: $115,000
  • Duration: 2 years (extension granted)
  • Location: The University of Adelaide, Flinders University, the Garvan Institute of Medical Research 
  • Status: Active
  • Start date: August 2021

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