Cure Sanfilippo Foundation awarded Jan Nolta, PhD, Director of UC Davis Stem Cell Program, University of California Davis, Institute for Regenerative Cures to engineer mesenchymal stem Cells (MSCs) to produce sulfamidase for intrathecal treatment of Sanfilippo Syndrome (MPS III).
Project Summary: This study aims to evaluate the use of non-embryonic mesenchymal stem cells (MSCs) for delivery of sulfamidase, the deficient enzyme in MPSIIIA, into the spinal fluid compartment.
MSCs will be gene modified to overexpress a normal copy of the SGSH gene (the MPSIIIA gene) and compared to unmodified MSCs.
In order to administer human MSCs to the mouse model, an immunodeficient strain of the MPSIIIA mouse model will be created.
Once complete, this new mouse model will be available for the scientific community at large.
The approach to use human MSCs to deliver enzyme, offers the possibility to deliver enzyme in a steady and physiologic fashion in the brain.
In addition, MSC-based delivery could avoid issues of pre-existing neutralizing antibodies that are inherent in AAV based gene therapies.
Due to the relative immune privilege of MSCs, they could be re-dosed with less concern of antibody development.
MSCs also inherently secrete neuroprotective and neurotrophic factors which could be beneficial in this neurodegenerative disease.
Update April 2017: MSCs have been gene-modified. Characterization of their enzyme expression is underway. An immunodeficient MPSIIIA mouse model is being cross bred and expanded for adequate study numbers after which animal dosing will begin.
Start Date: December 2015