A recent research effort pinpointed Interleukin-18 as a cause for Eosinophilic esophagitis, a lasting immune disease that afflicts children. The study indicates that blocking the secretion of this protein could potentially halt the disease, and suggests the already available drug, VX-765, could be a possible remedy.
Eosinophilic esophagitis was only recognized as a separate condition in the 1990s. Now, decades later, we may be on the brink of discovering a therapy.
A fresh research project from Tulane University has uncovered a potential treatment for a chronic immune disorder that may stop children from eating.
Eosinophilic esophagitis (EoE) is activated by food allergies or inhaled allergens, leading to an accumulation of a certain type of white blood cell, eosinophils, in the esophagus lining. This results in the esophagus becoming shorter and the esophageal wall thickening, making swallowing a challenge and causing food to become lodged in the throat.
Disease Frequency and Newly Discovered Origin
The disease is estimated to affect 1 in 2,000 adults but is more common in children (1 in 1,500), where symptoms are often more challenging to identify and pose increased risks as problems with feeding can lead to malnutrition, weight loss, and stunted growth.
The groundbreaking study, published today (July 31) in the Communications Biology journal from Nature, discovered that the disease is prompted by Interleukin-18 (IL-18), a protein associated with the inherent immune response, leading to inflammation when overproduced. When an allergen from food enters the body, it activates a pathway that regulates the innate immune system, releasing proinflammatory proteins such as IL-18. This results in eosinophils production, causing harm to the esophagus.
Uncovering Potential Treatment
The research demonstrated that effectively blocking this pathway, known as the NLRP3 pathway, and the release of IL-18, prevented the onset of EoE from both food and airborne allergens.
“This is a prominent and serious condition in children and its incidence is rising, as it is closely linked with food allergens which are also increasingly prevalent,” said lead researcher Dr. Anil Mishra, head of the Eosinophilic Disorder Center at the Tulane University School of Medicine. “In this research, we demonstrate that after treating the condition in animals, the disease is completely eliminated and remains in remission.”
Impact of the Study
These findings are significant for a disease that wasn’t identified until the 1990s. For a long time, EoE was wrongly diagnosed as gastroesophageal reflux disease (GERD), despite the fact that GERD medication proved ineffective in treating EoE. This research also overthrows decades of understanding that Th2 cells were the main culprits in causing EoE.
“Given the scarcity of data about the mechanisms and treatment options for EoE, we believe the proposed studies are of great relevance and have the potential to significantly influence the understanding of the role of the NLRP3-IL-18 pathway in the start of EoE development,” said Mishra.
Looking Ahead
The study highlighted an already existing drug, VX-765, as an inhibitor that could serve as a possible treatment in humans. Importantly, this inhibitor would only eliminate the harmful eosinophils generated and modified by IL-18, without affecting white blood cells produced by IL-5, a protein crucial for maintaining innate immunity.
The next step to verify the effectiveness of the treatment would be a clinical trial, said Mishra.
Citation: “Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis” 31 July 2023, Communications Biology.
DOI: 10.1038/s42003-023-05130-4
Table of Contents
Frequently Asked Questions (FAQs) about Eosinophilic esophagitis treatment
What is Eosinophilic esophagitis (EoE)?
Eosinophilic esophagitis (EoE) is a chronic immune system disease that is often triggered by food or airborne allergens. It causes eosinophils, a type of white blood cell, to accumulate in the esophagus lining, leading to a shortening of the esophagus and thickening of the esophageal wall. This makes swallowing difficult and can cause food to get stuck in the throat.
What is the prevalence of EoE?
EoE occurs in approximately 1 in 2,000 adults. However, it more frequently affects children, with an estimated prevalence of 1 in 1,500. Symptoms in children can be harder to diagnose and pose greater risks, as difficulty in feeding can lead to malnutrition, weight loss, and poor growth.
What triggers EoE?
The study found that EoE is caused by a protein called Interleukin-18 (IL-18), which is involved in the innate immune response. When food allergens enter the body, they activate a pathway responsible for regulating the innate immune system, leading to the release of proinflammatory proteins like IL-18. This results in the production of eosinophils which damage the esophagus.
How might EoE be treated according to the new study?
The study suggests that inhibiting the release of IL-18 could prevent the development of EoE. It identified an existing drug, VX-765, as a potential treatment for this purpose.
What are the next steps for this potential treatment?
The next step for this potential treatment is to conduct a clinical trial to determine its effectiveness in treating EoE in humans. The study has found that VX-765 successfully inhibits the pathway leading to the release of IL-18, preventing the onset of EoE from both food and airborne allergens.
More about Eosinophilic esophagitis treatment
- Communications Biology Journal Article
- Overview of Eosinophilic Esophagitis (EoE)
- About the drug VX-765
- More about Tulane University School of Medicine
- More on Dr. Anil Mishra’s research
5 comments
Science is amazing, isn’t it? One moment, we think we know everything, the next moment, we discover we were wrong all along. I mean, they used to think Th2 cells were causing EoE, and now it’s IL-18.
so they’re saying that they’ve found the cause and potential cure of a disease that was identified just 3 decades ago… mind blowing. science never ceases to amaze me.
Wow! Huge breakthrough if this is true. My cousin has this disease, and it’s been so tough for him and his family. fingers crossed for the clinical trials, hope they’re successful.
This is incredible news! And to think the drug already exists – just hope the trials go smoothly. More power to Dr. Mishra and his team.
If VX-765 works, it would be life changing for so many kids, including my daughter. So many meals have turned into battles with this disease, praying for positive results.