Peter Deak didn’t start graduate school intending to study his own disease.
But after spending the first two decades of his life scouring ingredient labels, Deak couldn’t help but be intrigued when he came across the work of a professor named Basar Bilgicer. The University of Notre Dame chemical engineer was in the midst of a project that could someday help the millions of people who—like Deak—are allergic to peanuts.
Years later, research conducted by Deak, Bilgicer, and their colleagues, published today in the journal PNAS, suggests that patients’ life-threatening reactions to peanut proteins might yet be preventable. Through the development of a chemical compound that incapacitates only cells that react to peanut proteins, their team might now have a new way to effectively deafen the immune system to these dangerous allergens.
“Our method is a high precision tool that can block the responsible [immune molecules] and nothing else,” Bilgicer says. “Hopefully, that means it will start working from day one.”
Though the technology is not itself a cure, it could curb the dangerous responses that often follow exposure to trace amounts of peanuts. It also has not undergone safety testing in humans. However, the team’s strategy, which can be adjusted to accommodate other immune triggers, could someday help combat other debilitating conditions, such as hay fever or autoimmune diseases.
“The versatility is pretty exciting,” says Onyinye Iweala, a researcher and physician at the University of North Carolina School of Medicine’s Division of Rheumatology, Allergy, and Immunology who was not involved in the study. “We now have a potential tool that can be targeted toward whatever allergen someone is allergic to.”
Food allergies are on the rise, but no preventative treatments are currently available in the clinic. Those plagued by peanuts and other food allergens still rely mostly on avoidance, many keeping their EpiPens always within reach. “It’s been an okay way to live,” Deak says, “but I don’t want to have worry about there being trace amounts in something. Growing up, that was a great cause of stress.”
That’s pretty understandable, given that peanut allergies can be deadly: Even a brief exposure to peanuts can cause hives, wheezing, nausea, and, in the most severe cases, anaphylaxis.
These allergies are essentially the immune system’s overzealous reaction to peanut proteins, wherein molecules called antibodies misidentify them as a threat. In the presence of peanut protein, antibodies can prompt mast cells—another type of immune foot soldier—to churn out gobs of histamine and other compounds that cause a range of inflammatory symptoms like redness, swelling, and itching.
Therapies to subvert these symptoms are currently in various stages of development, including oral medications and skin patches that gradually expose patients to tiny amounts of peanut protein until their immune systems grow accustomed to it. But these so-called immunotherapies have yet to hit the market. Even if they do, not all patients stand to benefit, Iweala says. Some patients don’t respond to the treatment, and others are so sensitive to peanuts that they’re imperiled by even the most minute doses.
Deak and Bilgicer’s research might offer a more palatable alternative. Rather than retraining the immune system to tolerate peanuts, their team’s method directly targets the crux of the allergic reaction: the catastrophic rendezvous between peanut and antibody.
Peanut proteins have dozens of potentially allergenic surfaces, but by screening each of them against a battery of immune cells taken from allergic patients, the team found that just two were responsible for most of the reaction.
They then designed a pair of compounds, each containing two crucial ingredients: one that resembled a piece of peanut protein to target the molecule to the correct antibody, and another that would permanently secure it to the antibody’s surface. This stealthy peanut impersonation allowed the molecules to latch on to antibodies in place of actual allergens—all without prompting an actual immune response. With the reactive cells taken out of commission, peanut proteins could then pass peacefully by.
The researchers next administered the two compounds to mast cells isolated from 16 allergic individuals (including Deak, though he didn’t test his own samples). To their surprise, the treatment silenced mast cells from all but two individuals—even after the cells had been dosed with peanut extract.
“We initially assumed we’d have to make [a new cocktail] for every single patient,” Deak says. But mast cells from most individuals seemed to respond similarly—suggesting that the team’s technology could have wide applicability.
“This is a great way of approaching a complex problem,” says Sarita Patil, an allergy researcher and clinician at Massachusetts General Hospital who has worked with Bilgicer’s group, but did not contribute to the study. “There are other subtleties of the disease, but this [interaction] is fundamentally what drives the disease. If we can shut that down, it could help a lot.”
The team’s ultimate goal is to commercialize an injection or pill that could prevent serious reactions to unexpected peanut encounters when administered once or twice a month.
By dampening the sensitivity of patients to small doses peanuts, the treatment could even increase the number of individuals who stand to benefit from immunotherapy, Bilgicer says.
But both of those possibilities are a long way off. Though the compounds appeared safe when injected into mice, the formulation has yet to be tested in humans, where it could still have unexpected side effects, says Vinidhra Mani, an immunologist at Harvard University who was not involved in the study. There’s also no guarantee the drugs will reach their intended targets—mast cells, which reside in the gastrointestinal tract, airway, and skin—when they have to first wade through the rest of the body.
Additionally, with only 16 patient samples, it’s hard to capture the diversity of individuals with peanut allergies, some of whom might not respond to these two compounds alone, Iweala says.
But Bilgicer remains optimistic. He hopes to next test samples from a larger population that includes people of all backgrounds. Even if there’s a range of sensitivities to different peanut allergens, the molecules are malleable, he says. By simply swapping out which allergens they mimic, future drugs could even be tailored on a patient-by-patient basis.
This also means peanut proteins aren’t the only options on the menu. Through the same chemical switcheroo, the technology could also be applied to other allergens, like pollen, or even the triggers of autoimmune disease. This “plug-and-play” feature could hold enormous promise, Iweala says. “The possible implications in that realm are going to be a huge. And that’s something to get excited about.”