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Neural Stem Cells for Sanfilippo Syndrome

November 30, 2019

Cure Sanfilippo Foundation has committed funding for a multi-year grant to Karl Johe, PhD, of ReMotor Therapeutics, Inc., to explore the therapeutic benefit of transplanting human neural stem cells engineered to overexpress and secrete SGSH into the brain of patients with Sanfilippo syndrome (MPS IIIA). The ultimate aim of the proposal is to launch a Phase 1/2 clinical study.

The therapeutic approach transplants human neural stem cells engineered to overexpress and secrete SGSH into the brain of MPS IIIA patients, which are taken up by the host cells and replace the missing enzyme. Thereby, reversing the disease course.

In a pilot study supported by Cure Sanfilippo Foundation in collaboration with the teams at UCDavis and Neuralstem, a conditionally immortalized human neural stem cell line was genetically engineered to overexpress SGSH (HK532.SGSH). The pilot cell line produced about 10-fold higher enzyme activity in the conditioned media than the non-gene therapy modified cells. This promising data has provided a basis for progressing toward further preclinical and clinical development.

This program and the clinical translation of gene modified neural stem cells for Sanfilippo syndrome (MPS III) would be the first of its kind. In addition to a cell-based enzyme replacement delivery, the inherent qualities of neural stem cells have the potential to offer a neurorestorative/neurosupportive benefit as well. This is particularly relevant for patients who are already symptomatic, which are the majority of children diagnosed.

“Moving beyond isolated enzyme restoration and into therapies that offer regenerative potential is critical to patients living with Sanfilippo syndrome and many other neurodegenerative diseases today. ReMotor’s unique approach offers an exciting opportunity to address the long term, multi-faceted needs of our children,” said Dr. Cara O’Neill, Chief Science Officer for Cure Sanfilippo Foundation.

The neural stem cell therapy expects to deliver the enzyme diffusely throughout the brain, stably and continuously for the patient’s life. Because the cells are administered directly into the brain, this approach avoids limitations experienced by other investigational therapies in getting drugs across the blood-brain barrier.

“I am extremely honored to receive this precious support from Cure Sanfilippo Foundation. Time is of the essence. I pledge to move the program to the first clinical trial as expeditiously as possible,” said Karl Johe, PhD, of ReMotor Therapeutics, Inc.

“The accepted premise is that neurologic disease cannot be reversed, especially in Sanfilippo syndrome (MPS III). Our children deserve to have champions who challenge this assumption and explore how we can help them better,” said Dr. O’Neill.

Project Updates
December 2020:

Optimized construct of the SGSH transgene to enhance expression, secretion and uptake of the enzyme has been completed.

April 2021:

A proof of concept study has been completed to determine feasibility of the technical delivery approach and volume of dosing into a large animal model. Information gained will be carried forward to inform next steps in therapeutic development.

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