“I remember telling my daughter Jori, when she was 14 years old, that she would not be able to eat food anymore,” recalls Ellyn Kodroff. “We sat at the kitchen table and sobbed as she took small sips of the vile-tasting formula, the only thing she could now have.”
Jori, now 20, has an eosinophilic gastrointestinal disorder (EGID). She and her parents travel to Cincinnati Children’s from Chicago every three months so that she can be treated by the Cincinnati Center for Eosinophilic Disorders (CCED), led by Marc Rothenberg, MD, PhD.
Cincinnati Children’s has become the acknowledged leader in treating and studying eosinophilic disorders – newly recognized conditions in which the body’s immune system treats food as a harmful entity, a foreign invader.
In response to food, the body rapidly produces too many immune cells called eosinophils. The cells attack the pathway that food takes – esophagus, stomach, intestines and other organs.
The eosinophils trigger chronic inflammation, pain and tissue damage. Individuals with EGID suffer from growth problems, stomach cramps, vomiting and diarrhea, and have trouble swallowing.
Some patients do well if they eliminate specific foods from their diet. Others are forced to stop eating all food and live on a liquid formula diet. The social, emotional and psychological effects can be staggering.
“Food is far more than just nourishment,” says Karen Philip, whose 12-year-old daughter, Grace, lives with an EGID. “It is an expression of our cultures and traditions. To have to view something so life- and soul-sustaining as a physical threat is daunting and, at times, exhausting.”
Deciphering the Mystery
A growing number of patients around the world face the challenge of living with and finding care for eosinophilic conditions. In the last decade, rates of many types of allergic diseases have skyrocketed. EGIDs now affect as many as one in 1,000 people. Though they are more common than inflammatory bowel disease and Crohn’s disease in children, EGIDs are not yet as widely known and are often misdiagnosed.
During a recent orientation session for new patients at the CCED, several families talked about their difficulties of finding expert care: “My doctor had only seen one other patient with this condition,” said one. “You’re kind of a mystery,” said another.
Cincinnati Children’s is at the forefront of deciphering the mystery by bringing eosinophilic disorders to the attention of the medical community, as well as conducting research to understand these conditions and advance care.
The work began in 1999, with one child.
Gastroenterologist Philip Putnam, MD, had a new patient in clinic. A biopsy sample of the child’s esophagus showed a lot of eosinophils.
He consulted with Dr. Rothenberg, director of the Division of Allergy / Immunology, who had done extensive basic research on eosinophils and their role in triggering allergic inflammation.
That first patient at Cincinnati Children’s was soon followed by others. Dr. Putnam and Dr. Rothenberg started holding a combined clinic and meeting to talk about what they were seeing. Soon pathologist Margaret Collins, MD, joined their team.
At the time, there had been only a few reports in medical journals about patients who were thought to have reflux disease but did not respond to medication and had elevated eosinophils. Not much was known about the condition.
The Cincinnati Children’s team wanted to understand more about these mysterious conditions: How to recognize them. How to diagnose them. The underlying biological pathways. How to make life better for patients who suffer with them.
From that small beginning, a comprehensive patient care and research program grew. It was the first of its kind anywhere.
Partnering to Advance Research
Linking clinical and research expertise was critical to the program’s success. “We’d be flying blind without the basic research,” Dr. Putnam points out. “We’d only be able to look at the end of the chain – the cells under a microscope. We wouldn’t understand the processes.”
As with any new research endeavor, securing funding to pursue new ideas was vital. In addition to traditional federal research grant funding, the partnership and investment of private donors proved essential to advance the study and care of EGIDs.
From hosting small fundraisers, to securing large-dollar support from nonprofits and foundations, to creating advocacy groups and testifying before Congress, the EGID community quickly established itself as an integral part of the CCED team.
The Kodroff family launched the Campaign Urging Research for Eosinophilic Disease (CURED), a national advocacy organization dedicated to raising public awareness of EGIDs and funds for research to cure it. The Buckeye Foundation, which is managed by the Philip family, also supports the CCED’s work. “It was a smart investment,” says Karen. “Dr. Rothenberg had the infrastructure needed to make a meaningful impact on the disease. We knew our investment would yield results.”
These two groups have become transformational partners, donating more than $4 million to advance the study and care of EGIDs at Cincinnati Children’s.
“Witnessing their huge commitment is a tremendous inspiration for our team,” says Dr. Rothenberg.
“Their partnership allowed us to pursue new ideas, often less conventional and more far-reaching than would be acceptable to typical funding agencies.”
Transforming the Landscape
Today the CCED is the world’s largest, most experienced clinical program for EGIDs, and the most productive research center.
It has seen more than 1,000 children and adults since 1999.
Families come from across the country and around the world seeking hope, healing and a better quality of life.
The center has brought major research discoveries from the laboratory bench to the clinic – transforming the landscape for patients living with eosinophilic disorders.
First, the CCED’s research in mouse models clarified the nature of these diseases. “Esophagitis used to be thought of as only acid reflux related,” says Dr. Rothenberg. “Our early studies provided a new paradigm, which subsequently has been accepted – that esophagitis could be an allergen-driven inflammatory process.”
This discovery led to a now widely practiced treatment approach: anti-inflammatory drugs for eosinophilic esophagitis.
The CCED conducted the first controlled clinical trial to test this approach. Today, two anti-inflammatory drugs are routinely used to control symptoms, and others are under development.
In another important contribution, the CCED advanced understanding of the genetics of EGIDs.
The CCED’s patient data, along with information compiled from its web-based patient registry, revealed that the disease occurs in families, suggesting that genetics has a role.
In fact, as EGIDs are better understood, many adults – including the parents and relatives of some of our pediatric patients – are finally being diagnosed after a lifetime of struggling with an unrecognized condition.
The CCED team has done pioneering research to decipher the genetic underpinnings of eosinophilic disorders. Dr. Rothenberg’s lab identified and defined the role of several genes and proteins involved.
These discoveries are fueling research for another promising treatment approach: antibodies against the proteins IL-5 and IL-13. Dr. Rothenberg led the first trials of anti-IL-5 and anti-IL-13. Several companies are now pursuing these approaches.
Dr. Rothenberg’s team also has developed a molecular-based diagnostic test for the disease. The test is currently being commercialized so that it can be available to patients everywhere.
Thanks to these and other achievements, doctors are better able to reduce patients’ eosinophil levels and control the disease.
Jori is now able to eat a few foods. Her college accommodates her very restricted diet by making her individualized meals with foods that are safe for her.
Moving to the Next Level
“The partnership of philanthropists helped us bring three major findings from the bench to patients,” says Dr. Rothenberg. “Their investment helped us build the clinical research enterprise necessary for truly meaningful translation of our findings to patients.”
But more needs to be done to improve outcomes for those who live with EGID.
“We’re making groundbreaking discoveries, but we still understand too little,” Dr. Rothenberg says. “A recent study by our group showed that children with EGID have the lowest quality of life compared with a wide number of other common pediatric chronic diseases. It’s humbling to see the degree of patient suffering despite all that we’re doing. We need to bring this whole field to a higher level – and we’re well positioned to do that.”
Dr. Rothenberg is convinced that “modern genetic approaches give us the technical capacity to begin to understand why people develop the disease – and that will help us develop better diagnostic tests and treatments, and ultimately find the cure.”
The patients and philanthropists who have run this race with him look forward to the day when they will cross the finish line together.
“I believe Dr. Rothenberg will find a cure,” Ellyn Kodroff says. “Then Jori and all the others suffering will have the opportunity to eat and enjoy life again.”