Sanfilippo Syndrome involves the accumulation of heparan sulfate sulphate in the body, resulting in progressive mental and physical deterioration. One therapeutic approach under investigation involves substrate reduction therapy (SRT), which aims to reduce the initial production of heparan sulfate. As a result, there would be less build-up of heparan sulfate over time, helping to slow disease progression and reduce symptoms.
In 2016, Prof. Andreas Schulze of The Hospital for Sick Children in Toronto was awarded a translational grant, co-funded by Cure Sanfilippo Foundation and Sanfilippo Children’s Foundation (Australia), to screen more than 7,100,000 potential SRT drugs for Sanfilippo and other MPS disorders involving heparan sulfate accumulation. Prof. Schulze and his team found nine potential drug candidates to further study.
The Foundations funded an extension grant in 2020 to further characterize the nine potential drug candidates for their ability to specifically inhibit NDST1 enzyme activity. The enzyme NDST plays an important role in the production of heparan sulfate. By targeting NDST, it may be possible to reduce heparan sulfate production and improve symptoms in Sanfilippo and other MPS disorders involving heparan sulfate accumulation.
Schultze’s team have completed that extension research and confirmed that one of the candidates can successfully inhibit NDST1 enzyme activity.
The team will continue working on these drug candidates, using them either alone or in combination to determine the best NDST1 inhibitors, and additional experiments will be undertaken to confirm the effects of the drugs and the best candidates for translation towards clinical trials. As the drugs help to reduce heparan sulfate production, they have potential application for Sanfilippo and other similar diseases, including Hunter and Hurler syndromes.
“It is through the generous donations from people around the world that the Foundation is able to fund critical, pioneering research,” said Foundation President & Co-Founded Glenn O’Neill. “We are very thankful for Professor Schultze, his team, and all the other researchers and clinicians devoting their time to helping children with Sanfilippo Syndrome. Together, we are moving closer and closer to a treatment every day.”