Improving delivery of gene therapy to brain for Sanfilippo Type C

The Sanfilippo Children’s Foundation has awarded AUD$90,000 towards a project led by Dr. Brian Bigger at the University of Manchester. This innovative project, entitled Improving delivery of gene therapy to the brain for Sanfilippo Type C, will investigate the best way to deliver gene therapy to the brain for Sanfilippo Type C (MPS IIIC).

Sanfilippo Type C is more challenging to treat than other subtypes because the enzyme that is missing – HGSNAT – anchors itself inside the cells of the brain and it cannot travel to neighbouring cells and treat them. For this reason, achieving maximum and even distribution of gene therapy throughout the brain is essential for gene therapy of Sanfilippo Type C to be effective.

Dr Bigger’s research group has already developed a gene therapy that consists of the HGSNAT gene delivered by a harmless modified virus called AAV. This has proven successful when injected into the brains of mice with Sanfilippo Type C, but although mouse brains were corrected, the correction was localised around the injection site.

The first aim of the project will be to determine the most effective type of AAV that will infect a wide range of different brain cell types. They will study the distribution of different types of AAV in a mouse model.

Secondly, they will explore the best method of injection into the brain using state-of-the-art computer modelling of fluid flow in the brain. They aim to determine the most effective needle size and flow rate to distribute the gene therapy throughout the brain.

The results of this project will be used to inform further preclinical studies to optimise the gene therapy method in preparation for a clinical trial, which if all goes well, could start within the next five years.

This project is being co-funded by the Sanfilippo Children's Foundation together with Jonah's Just Begun in the USA and the H.A.N.D.S consortium which represents eight global non-profit medical research foundations that work together to fund MPS IIIC research.

Michelle Morrice, Australian mother to ten-year-old Alec who has Sanfilippo Type C, said: “When I heard the news of this project it felt like I was no longer looking down a tunnel just seeing darkness, now I can see the slightest glimmer of light.  I am not unrealistic about the future of my son but to have even one person striving for his life fills me with such HOPE and gives me so much motivation to continue raising funds so that Dr. Bigger can continue to fight for these rare children.”

Jill Wood, co-founder of Jonah's Just Begun in the USA commented: “Jonah’s Just Begun along with our consortium H.A.N.D.S. is very pleased to receive support from the Sanfilippo Children’s Foundation on this project.  H.A.N.D.S. has been funding this program with Dr. Bigger's lab at the University of Manchester for six years now. MPS IIIC, does not have a treatment as of yet, but we are very close to taking this program to clinical trial.  With the support of our friends at the Sanfilippo Children’s Foundation, we will be able to get there faster."

Dr. Bigger said: “Recent trials in MPS IIIA and MPS IIIB have highlighted how hard it is to treat Sanfilippo and gain maximal enzyme distribution even with cross-correctable enzymes. Our work is critical to be able to scale up AAV gene therapy into the human brain for diseases like MPS IIIC where enzyme cannot move between cells. We aim to improve the distribution of AAV vectors in the brain so that ultimately we can use this as a therapy in patients with MPS IIIC and beyond."

The results of this study may also be applicable to other neurodegenerative conditions.

Dr. Bigger is Group Leader of the Stem Cell & Neurotherapies Lab at Manchester University. The group works on pathology, diagnosis and clinical development of treatments for neurodegenerative lysosomal storage diseases and glioblastoma, with expertise in the development of drug, gene and cellular therapies. The first therapy developed in the lab (substrate reduction therapy for MPS III) entered phase III clinical trial in mid-2014, with stem cell gene therapy for MPS IIIA licenced in 2016 and expected to be in trial shortly. 


Project Summary 

  • Chief Investigator: Dr. Brian Bigger
  • Project Title: Improving brain delivery of adeno-associated gene therapy vectors for the treatment of MPS IIIC and other neurodegenerative diseases 
  • Amount: $90K (1 year)
  • Location: University of Manchester,
  • Status: Completed (technology licenced to Phoenix Nest)