Grant Award Details
To enable an FDA pre-IND meeting for an allogeneic "off-the-shelf" human embryonic stem cell (hESC)-derived treatment for enteric neuropathies
Grant Application Details
- ASCENT- Advanced Superdonor Cellular Enteric Neuropathy Therapy
ASCENT - Advanced Superdonor Cellular Enteric Neuropathy Therapy, is a donor progenitor cell population that replaces the enteric nervous system.
Area of Impact
ASCENT would treat enteric neuropathies including Hirschsprung disease and total intestinal aganglionosis which currently have no direct therapy
Mechanism of Action
Our goal is to develop an allogeneic “off the shelf” cellular therapy to treat enteric neuropathies before surgical interventions are needed or to rescue patients in whom effects of the ENS defect persist. We propose to generate a cellular therapy from the starting material of “superdonor” human iPS cell lines. ASCENT - Advanced Superdonor Cellular Enteric Neuropathy Therapy, is a donor progenitor cell population that, after transplantation in vivo, replaces absent functional ENS components.
Unmet Medical Need
There are no direct therapies for enteric neuropathies and ASCENT would be the first cellular therapy for a broad class of severe disease including Hirschsprung disease and other enteric neuropathies that are morbid and mortal.
Successful Pre-IND meeting with the FDA
Major Proposed Activities
- Manufacture ASCENT to supply the proposed studies that will assess safety and efficacy
- Determine the optimal dosing of ASCENT as well as assess clinical safety
- Completion of nonclinical safety studies in order to schedule and complete a Pre-IND meeting
Enteric neuropathies cost the state of California hundreds of millions of dollars and cost the people of California more because of the severe problems including death that result from this class of diseases. This proposal benefits California in two ways: by supporting science and the industries in California that grow from ongoing investigation, but also by reducing the medical costs and suffering of patients with enteric neuropathic conditions with development of a novel and needed therapy.
- Am J Physiol Gastrointest Liver Physiol (2021) N-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo. (PubMed: 33881351)
- Exp Physiol (2018) Short-term and long-term human or mouse organoid units generate tissue-engineered small intestine without added signalling molecules. (PubMed: 30232817)
- J Pediatr Surg (2018) Stem cells for babies and their surgeons: the future is now. (PubMed: 30497818)
- Stem Cell Reports (2017) Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine. (PubMed: 28803915)
- Cold Spring Harb Perspect Med (2017) Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells. (PubMed: 28320829)
- Cell Stem Cell (2017) Created of Warm Blood and Nerves: Restoring an Enteric Nervous System in Organoids. (PubMed: 28061353)