New treatment for food allergies
Food allergies have been increasing at an alarming rate over the last few decades. Almost 8 percent of children under three years old and 4 percent of adults suffer from food allergies. When exposed to food allergens, most commonly peanuts, dairy, and shellfish, people with food allergies experience wheezing, itches, rashes and gastrointestinal distress—and in severe cases, deadly anaphylactic shock. Yet, despite the widespread problem, allergy treatments haven’t advanced much in decades and mostly focus on treating allergy symptoms.
Two types of immune cells — called mast cells and basophils — are the biggest culprits behind allergic reactions. When a patient encounters an allergen, let’s say peanut protein, the allergen binds to a type of antibody called immunoglobulin E, or IgE, that have occupied its receptors on mast cells and basophils. This stimulates the mast cells and basophils to release a storm of histamine, leukotrienes, prostaglandins and ultimately cytokines that provoke an allergic response to help exorcise peanut protein from the body.
Antihistamines—such as Benadryl, Claritin, Zyrtec and others—relieve allergy symptoms by blocking histamine receptors. Xolair, an engineered antibody, binds to human IgE and thus blocks it from triggering an inflammatory response. While effective in severe allergic asthma, it takes 6 – 8 weeks to fully kick in so it cannot be used for an acute attack. Classic allergy desensitization therapy, in which patients train their immune system to ignore increasing quantities of allergen via allergy shots is not only painstakingly slow, it also causes adverse events (AEs) in up to 95 percent of patients.
HISTAMINE RELEASING FACTOR
Dr. Toshiaki Kawakami discovered that histamine-releasing factor (HRF) serves as a “food allergy amplifier” and does as its name suggests: When activated by food allergens, HRF proteins bind to IgE and then both synergistically trigger the release of histamine and other allergy mediators from mast cells and basophils and enhance inflammation.
HRE-001 AND ITS POTENTIAL USES
Dr. Kawakami developed a peptide-based inhibitor (HRE-001), that blocks the activation of HRF. When administered orally to mice allergic to egg protein, HRE-001 ameliorated food-allergy symptoms such as gut inflammation, drops in body temperature and increased release of histamine and cytokines. The team also observed higher than normal levels of IgE antibodies extremely responsive to HRF (what immunologists call “HRF-reactive IgE”) in the blood of allergic mice, very similar to what is observed in children with egg allergies. This is a clear indication that HRF contributes to food allergy in humans like it does in mice. In addition, HRF-reactive IgE levels were reduced in patients who had undergone successful oral desensitization therapy to egg protein.
When administering just HRE-001 30 minutes prior to the allergen exposure, the allergic response is ameliorated in these animals. As this agent acts prior to mast cell activation by IgE, this product can protect against histamine release. Furthermore, the peptide is relatively quick acting so if one wants to go to dinner in a place where allergen (for example, peanut) exposure is potentially high, taking HRE-001 30 minutes prior to dining out would potentially be enough to mitigate an allergic response.
Another potential use for HRE-001 is to attenuate AEs associated with allergy sensitization strategies. Once Proof of Concept is confirmed with HRE-001 in both a peanut and ova allergic mouse model, we would like to introduce it to those companies that are in the process of receiving approval for their peanut allergy sensitization regimen. The combination of these therapies has the potential of significantly reducing the 95% AE rates observed during trials and improve compliance while being treated.
Taken together, these findings make HRE-001 a compelling biological for the treatment of food allergies.
Since HRE-001 that shuts down the allergic cascade before it reaches mast cells and basophils, it provides an alternative for people who don’t respond to antihistamines. Unlike Xolair, which takes weeks to become effective, HRE-001 acts within 30 minutes. This holds great promise for a prophylactic pill, which, when taken before eating at public places such as the school cafeteria or restaurants, could prevent the risk of anaphylactic shock when unexpectedly encountering a potentially deadly allergen.
Most importantly, it could be given in conjunction with classic immunotherapy to control adverse reactions during the desensitization process and to speed up the timeline. Currently the process is painstakingly long—not just months, but years—to treat a single allergy and many patients suffer from multiple allergies.