Eosinophilic Esophagitis

Eosinophilic Esophagitis and novel disease targets

Goal- Identify new therapy for treating eosinophilic esophagitis and food allergy.

Eosinophilic esophagitis (EoE) can occur in both children and adults and while the cause is not completely understood, food allergy likely plays a primary role in its development and severity.  EoE often presents with difficulty swallowing, food impaction, regurgitation or vomiting, and decreased appetite.  The disease is diagnosed through clinical symptoms, endoscopic characterization, and from tissue biopsies that have the characteristic eosinophil (white blood cell) infiltration within the esophagus tissue (depicted below).  The eosinophils may be the cell that causes the disease that includes inflammation and tissue fibrosis that does not allow the esophagus to function properly.  Another characteristic cell within the tissue is the mast cell that is known to play a significant role in allergic disease, both in IgE-mediated and IgE-independent processes that can contribute to the tissue fibrosis.  

One of the first therapeutic targets that we have begun to investigate is an immune mediator, Stem Cell Factor (SCF), which has been shown to contribute to tissue fibrosis and can directly activate both eosinophils and mast cells during chronic disease.  Our ongoing studies using a pre-clinical model of EoE have shown that by specifically blocking SCF the inflammation and tissue damage is significantly reduced, along with the number of eosinophils and mast cells in the esophagus. These results will allow our studies toward further development of new therapies that may be useful in the clinic for EoE and for food allergy responses.

The pathology of EoE is characterized by accumulation of eosinophils (stained red) in esophagus tissue depicted above 
 
The clinical signs of EoE listed above are exacerbated by the replacement of normal esophagus tissue with scar tissue that causes dysfunction and presents as fibrotic ring furrows as depicted above.