Generation of a novel preclinical animal model of Sanfilippo syndrome

The Sanfilippo Children’s Foundation and Fondation Sanfilippo Suisse have awarded an Incubator Grant to Professor Kim Hemsley at Flinders University. Professor Hemsley and Dr Adeline Lau aim to generate and characterise a new mouse model of Sanfilippo type A that will be used to progress the development of chaperone drugs.

Sanfilippo type A is caused by changes in both copies of the sulfamidase gene in an individual, leading to a deficiency of the sulfamidase enzyme. Different sulfamidase gene variants have been identified in patients with Sanfilippo type A but the R245H variant is one of the most common; for example, in Australasia, up to 31% of patients have this variant, while it is found in 58% of patients in The Netherlands.

Pharmacological chaperone therapy is a potential therapeutic avenue for those with particular types of gene changes known as missense mutations. The R245H variant is a missense mutation. However, the development of chaperone drugs for patients with R245H has been hindered by the lack of an appropriate animal model to test them in.

In this project, Professor Kim Hemsley and Dr Adeline Lau will drive the creation and characterisation of a new Sanfilippo type A mouse model with the R245H sulfamidase gene variant.

Once the new mouse model has been developed, the team will develop a method to genetically identify mice that carry the mutation and set up a breeding colony at Flinders University. They will then check that the mutation causes the expected signs and symptoms of the disease and compare it to the naturally occurring mouse model for Sanfilippo type A that is currently used for research with a different mutation known as D31N. Their work will include looking at the pathology in the brain and how fast it progresses, as well as behavioural tests for hyperactivity, anxiety, movement, coordination, and cognitive assessment. 

Following their extensive characterisation of the model, the team will share the findings and donate the R245H mouse to a global repository so it can be used by researchers worldwide to develop treatments for Sanfilippo.

“Researchers have been making progress in developing chaperone therapies for Sanfilippo and having this mouse available will assist in taking this research to the next level for pre-clinical evaluation,” said Dr Lisa Melton, Head of Research at the Sanfilippo Children’s Foundation. “The mouse model can also be used to test other potential therapies for Sanfilippo, and it will likely have a lasting impact on Sanfilippo research and the search for treatments.”

With over 20 years of experience in the Sanfilippo research field, Professor Kim Hemsley is interested in deciphering key disease mechanisms and evaluating therapy effectiveness for Sanfilippo syndrome. She is the head of the Childhood Dementia Research Group located at Flinders University in Adelaide, Australia. 

Project Summary

  • Project title: Generation of a novel preclinical animal model of Sanfilippo syndrome
  • Chief investigator: Professor Kim Hemsley 
  • Amount: $50,000 from Sanfilippo Children’s Foundation and $50,000 from Fondation Sanfilippo Suisse
  • Duration: 1.5 years
  • Location: Flinders University
  • Status: Active
  • Start date: December 2022

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