Optimising gene therapy for Sanfilippo Syndrome Type B

The Sanfilippo Children’s Foundation has awarded funding to a one-year gene therapy project, entitled, Gene therapy with intracranial delivery of capsid enhanced AAV NAGLU (MPSIIIB), led by Dr. Coy Heldermon at the University of Florida.

The Foundation is joined by Sanfilippo Initiative in Germany and Fundacja Sanfilippo in Poland as funding partners contributing a combined AUD$90,000 to this project.

This study aims to test several different modifications to existing gene therapy technology, along with different ways of administering it, to find the best combination to move forward to clinical trial.  

Gene therapy for Sanfilippo involves using a harmless virus to deliver a healthy copy of the gene that is faulty. Small clinical trials have already been completed or are underway for Sanfilippo types A and B, but it is widely accepted that further optimisation of gene therapy technology may be necessary to bring a highly effective therapy to the clinic. 

This project will test gene therapy in mice with Sanfilippo Type B using a type of virus called adeno-associated virus (AAV) to deliver the NAGLU gene into the brain and rest of the body. They will test different types of AAV that have had their protein shell altered to improve their ability to deliver the gene and reduce the chance of the immune system attacking it. They will also compare the delivery of the gene therapy by injection directly into the brain and into the spinal cord. 

The researchers will measure the success of the gene therapy by assessing the distribution of NAGLU production throughout the body and the ability of the mice to complete tests that measure their balance and agility. Sleep disruption is an early symptom of Sanfilippo and the same is true for Sanfilippo mice, so the researchers will also measure activity during the day (when they would normally be asleep) as an indication of disease progression.

“We wish to express our great appreciation to the families that care for children with MPS III and for the efforts they have made to raise money to find a cure. We believe the optimised AAV vector holds great promise to improve gene delivery to the central nervous system and provides a path to a viable commercial product in a short time frame. Thank you for your support,” said Dr. Coy Heldermon.

“This project has the potential to discover new gene therapy technology to move forward to clinical trial, and we look forward to following its progress.  Although we are optimistic about the gene therapy trials that are already underway for some types of Sanfilippo, we realise this is just the beginning, and our work is not done.  This research is important to ensure that second-generation therapies enter the drug development pipeline to deliver the best outcome for children living with Sanfilippo today and those born in the future,” said Megan Donnell Founder of Sanfilippo Children’s Foundation.

Dr. Heldermon is a medical doctor and has a Ph.D. in Biochemistry and Molecular Biology. His research expertise is in the use of gene replacement and stem cell therapies for the treatment of inherited disorders such as lysosomal storage diseases.

Project Update

Professor Coy Heldermon’s project Gene therapy with intracranial delivery of capsid-enhanced AAV NAGLU (MPS IIIB) has been completed. The project optimised an AAV8 viral delivery vector and tested its delivery via two different injection methods into the brain: a cisternal injection (into fluid-filled spaces at the base of the brain) and a parenchymal injection (into the brain tissue itself). Both injection methods resulted in a significant improvement in the lifespan and hearing of the Sanfilippo type B mice. The work completed in this grant contributed to a publication in the journal Archives of Stem Cell and Therapy, and a publication in the journal Human Molecular Genetics. The findings of this study may inform future gene therapy programs for Sanfilippo and other rare neurological diseases. Professor Heldermon has a patent pending for the technology and the technology is in further development at Lacerta Therapeutics, a pharmaceutical company that aims to develop gene therapy treatments for diseases that affect the central nervous system.

Project Summary

  • Chief investigator: Dr. Coy Heldermon
  • Project title: Gene therapy with intracranial delivery of capsid enhanced AAV NAGLU (MPSIII B)
  • Amount: $90K (over 1 year)
  • Location: University of Florida, USA
  • Status: Complete (technology licenced to Lacerta Therapeutics)
  • Start date: March 2017

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