Investigating potential stem cell therapy for Sanfilippo Type B

The Sanfilippo Children’s Foundation has awarded funding to a one-year stem cell therapy project, entitled, Neural and mesenchymal stem cell-mediated gene therapy for MPS IIIB, led by Dr Coy Heldermon at the University of Florida.

The researchers will investigate the potential of two different types of stem cells as a therapy for Sanfilippo Type B. If successful, this approach may be able to halt or slow the progression of Sanfilippo by supplying the enzymes that are missing and reducing inflammation in the brain. A major advantage over other potential therapies is that the stem cells may also be able to reverse the damage already caused prior to diagnosis and treatment.

The researchers will focus on two different types of stem cells – neural stem cells from the brain and mesenchymal stem cells that can be obtained from bone marrow and other tissues. Stem cell therapy has not yet been extensively studied in Sanfilippo, but the types of cells being investigated in the project are currently in clinical trial for other conditions such as multiple sclerosis and spinal cord injury.

This project will use stem cells from mice that have been bred to glow a green colour so that the cells can be tracked after transplant into recipient mice. The cells will first be genetically altered so that they produce large amounts of the enzyme that is missing in Sanfilippo type B (NAGLU) before being transplanted, alone or in combination, into the brains of mice with the condition.

After six months, the survival and distribution of transplanted stem cells and the production of NAGLU enzyme in the brain, spinal cord and other parts of the body will be assessed. The benefit of the therapy will also be monitored by tests which measure the balance and agility of the mice.

“My lab is honored by the funding for this exciting potential therapeutic approach. The use of stem cell approaches that do not require harsh conditioning regimens should allow better tolerated treatments,” said Dr Coy Heldermon.

“Although this is early stage research, and working with stem cells can be very challenging, we are excited to fund this research because if a type of stem cell, or combination of stem cells were found to be beneficial, it could lead to a breakthrough therapy for Sanfilippo. If successful, this approach could be applied to all types of Sanfilippo and other similar conditions,” said Megan Donnell Founder and Director of the Sanfilippo Children’s Foundation.

The Foundation is joined by Cure Sanfilippo (USA) as a funding partner contributing a combined AUD$90,000 to this project.

"We are excited to support Dr Heldermon's investigation of the use of non-embryonic stem cells in the Sanfilippo brain.  Typically by the time of diagnosis, children are already showing the detrimental effects of Sanfilippo Syndrome on their young brains.  Finding ways to restore health to the affected brain is a critical mission for patients living with neurodegenerative diseases today," said Cara O'Neill MD FAAP, Scientific Director of Cure Sanfilippo.

Project Update 

A/Prof Coy Heldermon and his colleagues have completed their Incubator grant awarded from the Sanfilippo Children’s Foundation and Cure Sanfilippo Foundation. Using a Sanfilippo type B mouse model, the team evaluated two different types of stem cells to see if they have the potential to treat Sanfilippo. 

The team used human-derived mesenchymal stem cells and mouse-derived neural stem cells that could be tracked via a fluorescent label. To determine the best type of stem cells and delivery method, they injected the stem cells into the brain via three different injection sites. Their results indicate that the body’s immune system helped to clear away the mesenchymal stem cells, which did not last as long in the brain compared to the neural stem cells.

After testing the different administration routes of the neural stem cells, the team found that a combined approach, with injections in parts of the brain and in its fluid-filled spaces, may be most effective in delivering this type of stem cell therapy.

The project overcame delays due to COVID-19, mouse breeding issues, supply chain delays, and delays in repairing key equipment for the project. The team presented their results in posters at the 2022 and 2023 WORLDSymposiums (The major global conference focussing on lysosomal storage diseases). They plan to continue their work on stem cells for Sanfilippo towards getting data to ultimately start a clinical trial for patients.

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 Summary 

  • Chief Investigator: Dr Coy Heldermon
  • Project Title: Neural and mesenchymal stem cell-mediated gene therapy for MPSIII B 
  • Amount: $90K (over 1 year)
  • Location: University of Florida, USA
  • Start date: March 2017
  • Completed