Recent advances in potential targets for eosinophilic esophagitis treatments

ABSTRACT

Introduction: Diagnostic and therapeutic strategies in eosinophilic esophagitis (EoE) are constantly evolving. Recently, the improved understanding of EoE pathogenesis has led to identification of a variety of other potential targets that have never been considered before.

Areas covered: In September 2019, we performed structured literature searches in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses to review new potential therapeutic approaches for EoE.

Expert opinion: The advent of omics disciplines has been helping in finding new molecular targets in EoE pathogenesis and may provide future guidance for deep phenotyping of the disease and therefore facilitate the possibility of personalized medicine. Interestingly, these new treatments should be focused on the restoration of epithelial barrier dysfunction, downregulation of specific molecular pathways of eosinophilic inflammation, and finally, prevention of esophageal remodeling. In this review, we highlight the most recent insights in EoE pathogenesis, which open new pathways for developing new therapeutic targets for clinical practice.

KEYWORDS:

• Eosinophilic esophagitis
• proteases
• fibrosis
• biologics
• treatment
• biologics

Article Highlights

• The improved understanding of EoE pathogenesis has led to the identification of a variety of other potential therapeutic targets.

• IL-13 has been shown to promote transcriptional changes of several key epithelial barrier regulatory genes and cardinal disease pathways. By targeting this molecule and its receptor, it will likely be possible to affect the inflammatory response and restore the epithelial barrier function.

• Considering the Th2 dysregulation in EoE, agents that are able to block Th2 cell, basophil, and eosinophil recruitment and activation are considered potential targets.

• The EoE fibrotic process represents the more challenging goal for the development of new molecules able to revert the disease process.

Author Contributions

All authors contributed to the conceptualization of the study, interpretation of study results, and editing of manuscript drafts. S.O. and N.P.A. should be considered as joint first author.

Declaration of Interest

S Oliva is a consultant for Ocean Farma and Medtronic. ME Rothenberg has been a consultant for Pulm One, Spoon Guru, Clostrabio, Celgene, Astra Zeneca, and Regeneron and has an equity interest in the first three listed and receives royalties from Reslizumab (Teva Pharmaceuticals) and UpToDate. ME Rothenberg and NP Azouz are inventors of patents owned by Cincinnati Children’s Hospital Medical Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One of the peer reviewers has disclosed that they have participated in the advisory boards of companies developing anti-IL 13 agents. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.