Research Collaboration with Mayo Clinic’s Arizona Campus: Working Together on a Cure for Eosinophilic Esophagitis
In order to understand the associations between food allergies, OIT, and EoE, the Center is collaborating with Drs. Matthew Rank and Benjamin Wright of Mayo Clinic’s Arizona Campus. Both research teams are very excited about working together to better understand EoE.
Eosinophilic esophagitis (EoE) is a disease characterized by inflammation and narrowing of the esophagitis (the tube connecting the mouth to the stomach). The disease is rare in the general population but more likely in those with food allergies (0.04% vs 4.7%, respectively). Symptoms vary with age and severity and include vomiting, abdominal pain, and difficulty swallowing (particularly dry or dense solid foods). In severe cases, the food can get stuck in the esophagus. EoE has been associated with poor growth in infants and toddlers due to their refusal to eat. On a molecular level, eosinophils (a type of immune white blood cells) are greatly increased in the esophagus and can be visualized through a microscope.
At the Sean N. Parker Center for Allergy and Asthma Research, Dr. Nadeau has successfully treated over 1,000 patients with food allergy over the last eight years with oral immunotherapy (OIT) and this newly emerging treatment has greatly improved the quality of life of those with food allergies. At the Center, we are constantly modifying treatment protocols and evaluating novel treatment strategies to improve safety and efficacy of desensitization to food allergies. OIT has been shown to be safe and effective for the majority of patients; however, the therapy has some side effects. As many as 50% develop digestive problems such as nausea, vomiting, and abdominal discomfort causing an estimated 20% to patients to discontinue treatment. Although some patients develop EoE with OIT, whether these abdominal symptoms are predictive of developing EoE or indicative of underlying EoE is unclear.
In order to understand the associations between food allergies, OIT, and EoE, the Center is collaborating with Drs. Matthew Rank and Benjamin Wright of Mayo Clinic’s Arizona Campus. Dr. Rank is chief of the Division of Allergy, Asthma and Clinical Immunology and Dr. Wright is an allergist and immunologist with expertise in food allergy and EoE. Both research teams are very excited about working together to better understand EoE.
‟We are extremely enthusiastic about our collaboration with Dr. Kari Nadeau and her team at Stanford University. We believe that our research collaboration focusing on adverse effects of immunotherapy with foods will lead to an improved understanding of how to prevent them in the future,” shared Dr. Matthew Rank.
We thank Kathy and Donald Levin, who through a generous contribution, made this research collaboration possible. Our aim is to understand the role of eosinophils in food allergy and improve safety of OIT by identifying those at risk of developing complications from OIT or developing treatments to mitigate or prevent these side effects. Some preliminary results through our joint collaboration were presented at the January 2018 Gordon Research Conference in Southern California.
"Dr. Nadeau is a pioneer in the food allergy field at Stanford University and Mayo Clinic is leading the way in medicine. It was a natural fit to bring these two world renowned institutions together for a collaboration. We are proud to bridge this relationship for science and research, hopefully making a lasting impact for many generations, as it has for our family," said Donald Levin.
Using cutting-edge molecular assays and sophisticated automated image analysis, Mayo Clinic has analyzed gastrointestinal (GI) tissue samples (obtained from patients who underwent long-term peanut-OIT at the Center) for eosinophil levels and activity in the GI tract before, after, and during different stages of OIT. The results indicate that half of the samples had high levels of eosinophils in the GI tract, even before the start of OIT and that in some patients they increased during OIT. Although it appears that in many individuals these increases during OIT are transient, some individuals go on to develop EoE. A 2014 study found that about 2.7% of patients undergoing OIT develop EoE. Further research to better identify biomarkers and patients in whom high levels of GI eosinophils lead to EoE would be valuable for personalizing treatments.
To further our understanding of the mechanisms underlying EoE, Mayo Clinic has engineered mouse models that mimic eosinophilic activity in a manner similar to humans. These novel mouse models are essential for determining the effects of novel therapies and for better understanding key genes and molecular pathways involved in EoE. The Center will work together with Mayo Clinic to test new therapies and evaluate their effects on eosinophils in these mouse models. These animal models are invaluable for further guiding scientists in developing protocols for clinical studies.
On the Horizon
The Center and Mayo Clinic are also working towards setting up a multi-center clinical study to evaluate the use of dupilumab, a biomolecule that has been approved by the FDA for treatment of adult patients with moderate-to-severe atopic dermatitis. Dupilumab has been shown to dramatically reduce the number of eosinophils in the GI tract in those with EoE and may be effective in reducing symptoms in select patients with GI symptoms. We are excited to evaluate this drug for EoE in clinical trials, which we plan to initiate at the end of 2018.
If you are interested in learning more about a specific trial or being screened for a trial at our Center, please join our registry at is.gd/snpregistry or email us at firstname.lastname@example.org.
By Vanitha Sampath
Vanitha Sampath received her PhD in Nutrition from the University of California at Davis. At the Sean N. Parker Center for Allergy and Asthma Research, as a medical writer and content manager, she enjoys being in the midst of groundbreaking research in asthma and allergy and is committed to communicating the scientific advances of the Center and spreading awareness of its mission and vision.