Background

Enteric nervous system (ENS) development and function are governed by a broad array of regulatory molecules that are only partially known. Disruption of signaling pathways from congenital or acquired defects results in varying degrees of pathology. Among congenital enteric neuropathies, Hirschsprung’s disease (HD) is the most common and is reported to arise from impaired migration of enteric neural crest cells (ENCCs) within the gut during fetal development, leading to functional obstruction from an inability to relax intestinal smooth muscle. Surgical resection of the distal aganglionic segment of intestine in HD decreases mortality but does not result in complete resolution of symptoms.

Neuropathy manifests as gastroparesis (1:4,000 live births), a frequent complication of diabetes, neurodevelopmental disorders, and muscular dystrophy. Medical therapy can control some of the symptoms of gastroparesis, such as chronic nausea, vomiting, abdominal pain, and malnutrition but does not address the root cause. Esophageal enteric neuropathy, or achalasia (1:100,000), is associated with the loss of innervation of the lower esophageal sphincter, whether idiopathic or due to parasitic infection, and is treated with partially effective surgical and endoscopic interventions that carry the risk of esophageal rupture and replacement. Enteric neuropathies also affect large numbers of patients via slow transit constipation (1:100), anal incontinence (<1:100) and chronic intestinal pseudoobstruction (1:2,000). In gulf war syndrome there is destruction of enteric nerves in returning soldiers from nerve agents.

Technology Overview

Novel cellular therapies derived from human induced pluripotent stem cells (hiPSCs), such as the stem cell line LiPSC-GR1.1 or other cell lines, stem cells, including embryonic stem cells (ESCs), universal cell lines, or pluripotent stem cells for the treatment of enteric neuropathies is provided herein. One embodiment provides a method to treat an enteric neuropathy comprising administering enteric neural crest cells (ENCCs) to a muscular wall of intestine in a subject in need thereof, wherein the ENCCs are differentiated from stem cells in vitro. One embodiment provides a composition comprising enteric neural crest cells (ENCCs) differentiated from stem cells in vitro and a cryopreservative.

Benefits

Cellular therapy outperforms surgical and other medical interventions.

Applications

Enteric neuropathies affect large numbers of patients via slow transit constipation (1:100), anal incontinence (<1:100) and chronic intestinal pseudoobstruction (1:2,000). Gastroparesis (1:4,000 live births), a frequent complication of diabetes, neurodevelopmental disorders, and muscular dystrophy.

Congenital enteric neuropathies, Hirschsprung’s disease (HD) (1:5,000 live births) is the most common.

In gulf war syndrome there is destruction of enteric nerves in returning soldiers from nerve agents.

Opportunity

Looking for partner to license the technology and collaborate on its development and commercialization.