Evaluation of disease-modifying drugs for attenuated forms of Sanfilippo

The Sanfilippo Children’s Foundation and Cure Sanfilippo Foundation have awarded an Incubator Grant to Professor Kim Hemsley at Flinders University. Professor Hemsley and her collaborators, Dr Siti Mubarokah (Flinders University) and Dr Nick Smith (Women’s and Children’s Hospital, Adelaide), will develop new cell models of the attenuated form of Sanfilippo type A and use the cells to screen a panel of FDA-approved drugs to see if they may have potential to be repurposed to treat attenuated Sanfilippo syndrome.

Some gene variants that lead to Sanfilippo can cause a more slowly progressing, attenuated form of the disease. In some clinical trials, people with Sanfilippo are excluded if they have a known attenuated gene variant, leaving these patients with even fewer treatment options.

Researchers frequently use disease models to study a disease and test potential therapies. In neurodegenerative diseases like Sanfilippo, ‘neuronal-like’ cell models are often created. These can be developed in the laboratory from skin cells collected from patients, which are ‘reprogrammed’ into stem cells and then into different brain cells. While this process generates a close model of living human nerve cells, it takes a few months to complete.

In this project, Professor Hemsley and her colleagues aim to create ‘photoreceptor-like’ cell models of attenuated Sanfilippo instead, using a more rapid direct method that generates the cells, in just over two weeks, rather than several months. Photoreceptor cells are cells in the retina of the eye that respond to light. The new photoreceptor-like cell models will be created from skin cells of patients with attenuated Sanfilippo type A previously collected in a project with funding from Sanfilippo Children’s Foundation and Perpetual Trustees.

Professor Hemsley’s laboratory and other groups have found heparan sulfate build-up and damage in eye cells in Sanfilippo. This suggests that eye cells could provide a useful model to screen drugs and see if the damage can be stopped or reversed.

Once the attenuated cell model is developed in this project, the team will examine the characteristics of the cells and then use them in a drug screen with a variety of FDA-approved drugs. Only drugs that are known to enter the brain from the bloodstream and act in the brain will be used in this project.

“Cure Sanfilippo Foundation is excited to support Prof. Hemsley’s novel strategy to develop photoreceptor-like cells for use in drug repurposing. Utilizing samples from patients with attenuated forms of Sanfilippo type A will bring a needed focus to this understudied population and could lead to an important step forward in the discovery of patient-centered therapeutics in Sanfilippo syndrome,” said Dr. Cara O’Neill, Chief Science Officer at Cure Sanfilippo Foundation.

“We are pleased to be collaborating with Cure Sanfilippo Foundation again to co-fund this project. With this rapid method to generate a model of Sanfilippo patients’ cells we hope that it can accelerate the process for screening and identifying potential treatments for Sanfilippo syndrome,” said Dr Lisa Melton, Head of Research at the Sanfilippo Children’s Foundation. “As the project will look at drugs that have already been approved for use in people, it may also expedite their path towards clinical trials.”

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: Swift in vitro evaluation of disease-modifying drugs for attenuated forms of Sanfilippo
  • Chief investigator: Professor Kim Hemsley 
  • Amount:  AU$60,750 from Sanfilippo Children’s Foundation and AU$60,750 from Cure Sanfilippo Foundation
  • Duration: 1 year
  • Location: Flinders University
  • Status: Active
  • Start date: February 2024

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