(CINCINNATI) – A recent research published in Nature Genetics has identified a new molecular and genetic pathway in the esophagus that leads to eosinophillic esophagitis (known as EoE), giving rise to potentially new therapeutic schemes for a mysterious and hard-to-treat food allergy.
To describe, EoE is basically a chronic inflammatory condition of the esophagus. This disorder is provoked by allergic hypersensitivity to some specific foods and by an over-accumulation in the esophagus of white blood cells known as eosinophils (part of body’s immune system).
Moreover, EoE can lead to a number of gastrointestinal disorders involving reflux-like symptoms, such as vomiting, tissue scarring, formation of strictures, difficulty in swallowing, fibrosis and some other medical problems.
The multi-institutional panel of researchers, who reported their results online, was governed by some scientists at Cincinnati Children’s Hospital Medical Center. Authors of the study recognized a molecular pathway in the esophagus, related to epithelial tissue that involved a gene known as CAPN14, which according to them, becomes significantly up-regulated during the disease process.
Furthermore, epithelial cells help in forming the membrane of the esophagus. According to scientists, as soon as these cells were brought in contact with a familiar molecular activator of EoE (which is an immune hormone known as Interleukin 13 or IL-13), it lead to significant stimulation of CAPN14. According to the researchers, this happened because of an epigenetic hotspot for EoE on the chromosomes of the cells.
Marc E. Rothenberg, MD, a senior investigator of the study, and the director of Cincinnati Children’s Center for Eosinophilic Disorders, said that CAPN14 encodes a particular enzyme in the esophagus, which is part of disease process, known as calpain14. As caplain14 can easily be inhibited and targeted by drugs, so the study gives rise to new therapeutic schemes for researchers.
Rothenberg further explained, “In a nutshell, we have used cutting edge genomic analysis of patient DNA as well as gene and protein analysis to explain why people develop EoE. This is a major breakthrough for this condition and gives us a new way to develop therapeutic strategies by modifying the expression of caplain14 and its activity. Our results are immediately applicable to EoE and have broad implications for understanding eosinophilic disorders as well as allergies in general.”
This study has come after years of research in EoE by the laboratory of Rothenberg, including the creation of new modeling programs for this disease, and large scale multi-institutional collaboration via the Food Allergy Researchers’ National Institutes of Health’s Consortium.
Rothenberg said that these results give rise to a new way for considering therapeutic options. This is because the enzyme calpain14 can easily be controlled by drugs. Hence, modifying the activity and expression of calpain14 may be possible.