A small study published in the journal JCI Insight on November 14, 2019, suggests that antibody treatment could help people with severe allergy to peanuts eat a small amount of peanut-containing food just two weeks later, without any ill effects. This seems to show that this is a safe, fast and effective treatment for food allergy.
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Food allergies afflict about 32 million Americans. These troublesome conditions may begin at any age, and hinder social activity as well as making food selection and preparation a cumbersome process. The only current treatment that cures people is oral immunotherapy, in which people eat very small amounts of the foods to which they are allergic, under medical supervision, in very gradually increasing doses, until their bodies adjust to the allergens. This process is called desensitization and may take up anywhere from 6 months to a year. At any point the individual may develop an exacerbation.
The current antibody treatment appears to be quite different.
The study and its findings
For the study, the scientists treated 14 adult participants, all of whom had severe allergic reactions to peanuts, with a single injection of the antibody. Another 5 people who had similarly serious allergies to the legume had a placebo injection.
About 73% of the antibody injection recipients were able to tolerate eating a small amount of peanut protein, namely, 275 mg (under medical supervision), in just 15 days from the injection. This is equivalent to the protein in a single peanut. None of the five patients who received placebo could tolerate the protein. At the 45th day, 7 people in the first group were retested, as well as the placebo group. 4/7 people in the first group continued to tolerate the protein, while no placebo patient could. In other words, the effects of the treatment persisted over several weeks.
Without having to expose the gastrointestinal tract to the allergen, these individuals developed tolerance to the offending protein. They also had lower levels of allergy-induced chemicals in their blood at day 15 compared to placebo recipients, in addition to other changes that indicated a downregulation of the immune system to allergens. The safety profile appears to be acceptable, with no serious adverse effects being reported.
The secret weapon
The magic bullet is a drug called etokimab, a drug that inhibits interleukin-33, which is a signaling molecule in the immune cascade of reactions that set off allergies. IL-33 is a trigger that is set off by exposure to a molecule to which the individual has developed an allergy, or hypersensitivity reaction, as it is called. When released, it switches on the production and release of another molecule called immunoglobulin E, or IgE, for short. This is a molecule characteristically found in people with allergies, localized in the mucosal tissue. It is involved in many aspects of the allergic reaction, such as itching of the throat and mouth, skin bumps and itching, shortness of breath and even, in the worst cases, anaphylaxis. Anaphylaxis is a sometimes fatal extremely severe allergic response to an often innocuous substance, which causes the blood pressure to plunge while the airways close off. The only effective and even lifesaving treatment is epinephrine, which arrests the reaction and opens the airways, also pushing the heart to beat harder while boosting the blood pressure back to normal levels.
In other words, IL-33 activation is like detonating a bomb. For this reason, etokimab is an extremely effective treatment because it quenches the whole reaction before it starts, defusing the bomb instantaneously. This is why this treatment is so promising – it can potentially inhibit all kinds of allergies since it acts on a common mediator, rather than inducing tolerance to one allergen at a time. It has already undergone testing in people with other allergic conditions such as asthma and eczema.
And even better, says researcher Kari Nadeau, “Although this is still in the experimental stages, we're delivering on the hope of testing a drug that won't be for one food allergy but for many, and for other allergic diseases, too.”
The scientists now want to repeat the study on a much larger group as well as try to identify characteristics that will differentiate those who will benefit from the treatment from those who are unlikely to. The optimal dosage and timing of the antibody must also be determined.
Sharon Chinthrajah, Shu Cao, Cherie Liu, Shu-Chen Lyu, Sayantani B. Sindher, Andrew Long, Vanitha Sampath, Daniel Petroni, Marco Londei, Kari C. Nadeau, Phase 2a randomized, placebo-controlled study of anti–IL-33 in peanut allergy, JCI Insight. 2019;4(22):e131347. https://doi.org/10.1172/jci.insight.131347, https://insight.jci.org/articles/view/131347