Food Allergy Research: Tackling a Complex Problem From Many Angles
As molecular biology research has become more sophisticated and personalized genetic testing has become more popular, some members of the food allergy community have asked us when genetic tests and treatments for food allergy will become available. In particular, food allergy patients and families have expressed hope that advances in gene editing and manipulation can soon lead to a cure.
We anticipate that the latest generation of molecular tools will drive advances in animal studies of food allergy. Researchers across the country, including many that receive support from FARE, are conducting experiments in mice to unlock the molecular details that underlie food allergy reactions. Allergist and food allergy investigator Dr. Hugh Sampson has noted that “over the years, we’ve cured a lot of mice of food allergy,” highlighting the difficulties encountered in translating a successful therapy in mice to a successful therapy in people. While research studies in mice yield some valuable insights, these studies alone have not revealed why food allergy has become increasingly common in recent years or provided timely treatments for patients managing food allergies today. This is because food allergy is not caused simply by genetic factors.
A new molecular tool, a technology called CRISPR, has received much attention as it makes it easier to add, remove or replace genes in chromosomes. CRISPR is now widely used in animal research and is being tested in experimental human gene therapies. For example, it has been used in mice to replace the damaged gene that causes cystic fibrosis in humans. By comparison, a CRISPR-based food allergy treatment has not been attempted. This is partly because multiple genes appear to be involved in food allergy, so altering a single gene will not cure food allergy. This problem is further complicated as the genetic elements that mediate food allergy vary between different individuals. Also, it is difficult to get the human immune system to stop attacking food allergens once food allergy starts. Therefore, genetically identical mice cannot adequately represent the complexity of food allergy in human patients.
There is substantial evidence that epigenetics – environmental factors that affect how and when genes are used to make proteins – appears to be the most important influence on food allergy risk. Genetically similar populations can have very different rates of allergic disease. Ashkenazi Jewish children who live in the UK are much more likely to develop peanut allergy than those who live in Israel, where babies routinely eat peanut foods. Likewise, Amish children who live in close contact with farm animals are much less likely to have asthma than Hutterite children who live away from farms, even though both populations share close ancestry. Also, the slow pace of genetic change in humans can’t explain the dramatic increase in food allergy prevalence that began in the mid-1990s.
Some, but not all, people with food allergies are able to tolerate significant doses of their allergen following immunotherapy. Many, but not all, children at high risk for peanut allergy are protected by early introduction of peanut foods. These differences, which suggest that food allergy may have several underlying causes, illustrate why human clinical trials are so important in developing food allergy therapies. In human trials of new therapies for food allergy, no approach has been successful in all patients. Therefore, individual responses to treatment must be evaluated in molecular detail, applying cutting-edge research tools to better understand approaches to treat food allergy.
While no simple genetic test or gene therapy for food allergy is likely to emerge in the near term, FARE remains committed to funding a wide range of human and animal studies in continuing to advance these efforts.
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A September 2017 study in Annals of Allergy, Asthma and Immunology reported that open oral food challenge (OFC) is a relatively safe procedure that offers benefit to patients.