A skin patch to treat peanut allergies teaches the body to tolerate the nuts
Ever since he was a baby, Sharon Wong’s son Brandon suffered from rashes, prolonged respiratory issues and vomiting. In 2006, as a young child, he was diagnosed with a severe peanut allergy.
"My son had a history of reacting to traces of peanuts in the air or in food,” says Wong, a food allergy advocate who runs a blog focusing on nut free recipes, cooking techniques and food allergy awareness. “Any participation in school activities, social events, or travel with his peanut allergy required a lot of preparation.”
Peanut allergies affect around a million children in the U.S. Most never outgrow the condition. The problem occurs when the immune system mistakenly views the proteins in peanuts as a threat and releases chemicals to counteract it. This can lead to digestive problems, hives and shortness of breath. For some, like Wong’s son, even exposure to trace amounts of peanuts could be life threatening. They go into anaphylactic shock and need to take a shot of adrenaline as soon as possible.
Typically, people with peanut allergies try to completely avoid them and carry an adrenaline autoinjector like an EpiPen in case of emergencies. This constant vigilance is very stressful, particularly for parents with young children.
“The search for a peanut allergy ‘cure’ has been a vigorous one,” says Claudia Gray, a pediatrician and allergist at Vincent Pallotti Hospital in Cape Town, South Africa. The closest thing to a solution so far, she says, is the process of desensitization, which exposes the patient to gradually increasing doses of peanut allergen to build up a tolerance. The most common type of desensitization is oral immunotherapy, where patients ingest small quantities of peanut powder. It has been effective but there is a risk of anaphylaxis since it involves swallowing the allergen.
"By the end of the trial, my son tolerated approximately 1.5 peanuts," Sharon Wong says.
DBV Technologies, a company based in Montrouge, France has created a skin patch to address this problem. The Viaskin Patch contains a much lower amount of peanut allergen than oral immunotherapy and delivers it through the skin to slowly increase tolerance. This decreases the risk of anaphylaxis.
Wong heard about the peanut patch and wanted her son to take part in an early phase 2 trial for 4-to-11-year-olds.
“We felt that participating in DBV’s peanut patch trial would give him the best chance at desensitization or at least increase his tolerance from a speck of peanut to a peanut,” Wong says. “The daily routine was quite simple, remove the old patch and then apply a new one. By the end of the trial, he tolerated approximately 1.5 peanuts.”
How it works
For DBV Technologies, it all began when pediatric gastroenterologist Pierre-Henri Benhamou teamed up with fellow professor of gastroenterology Christopher Dupont and his brother, engineer Bertrand Dupont. Together they created a more effective skin patch to detect when babies have allergies to cow's milk. Then they realized that the patch could actually be used to treat allergies by promoting tolerance. They decided to focus on peanut allergies first as the more dangerous.
The Viaskin patch utilizes the fact that the skin can promote tolerance to external stimuli. The skin is the body’s first defense. Controlling the extent of the immune response is crucial for the skin. So it has defense mechanisms against external stimuli and can promote tolerance.
The patch consists of an adhesive foam ring with a plastic film on top. A small amount of peanut protein is placed in the center. The adhesive ring is attached to the back of the patient's body. The peanut protein sits above the skin but does not directly touch it. As the patient sweats, water droplets on the inside of the film dissolve the peanut protein, which is then absorbed into the skin.
The peanut protein is then captured by skin cells called Langerhans cells. They play an important role in getting the immune system to tolerate certain external stimuli. Langerhans cells take the peanut protein to lymph nodes which activate T regulatory cells. T regulatory cells suppress the allergic response.
A different patch is applied to the skin every day to increase tolerance. It’s both easy to use and convenient.
“The DBV approach uses much smaller amounts than oral immunotherapy and works through the skin significantly reducing the risk of allergic reactions,” says Edwin H. Kim, the division chief of Pediatric Allergy and Immunology at the University of North Carolina, U.S., and one of the principal investigators of Viaskin’s clinical trials. “By not going through the mouth, the patch also avoids the taste and texture issues. Finally, the ability to apply a patch and immediately go about your day may be very attractive to very busy patients and families.”
Brandon Wong displaying origami figures he folded at an Origami Convention in 2022
Sharon Wong
Clinical trials
Results from DBV's phase 3 trial in children ages 1 to 3 show its potential. For a positive result, patients who could not tolerate 10 milligrams or less of peanut protein had to be able to manage 300 mg or more after 12 months. Toddlers who could already tolerate more than 10 mg needed to be able to manage 1000 mg or more. In the end, 67 percent of subjects using the Viaskin patch met the target as compared to 33 percent of patients taking the placebo dose.
“The Viaskin peanut patch has been studied in several clinical trials to date with promising results,” says Suzanne M. Barshow, assistant professor of medicine in allergy and asthma research at Stanford University School of Medicine in the U.S. “The data shows that it is safe and well-tolerated. Compared to oral immunotherapy, treatment with the patch results in fewer side effects but appears to be less effective in achieving desensitization.”
The primary reason the patch is less potent is that oral immunotherapy uses a larger amount of the allergen. Additionally, absorption of the peanut protein into the skin could be erratic.
Gray also highlights that there is some tradeoff between risk and efficacy.
“The peanut patch is an exciting advance but not as effective as the oral route,” Gray says. “For those patients who are very sensitive to orally ingested peanut in oral immunotherapy or have an aversion to oral peanut, it has a use. So, essentially, the form of immunotherapy will have to be tailored to each patient.” Having different forms such as the Viaskin patch which is applied to the skin or pills that patients can swallow or dissolve under the tongue is helpful.
The hope is that the patch’s efficacy will increase over time. The team is currently running a follow-up trial, where the same patients continue using the patch.
“It is a very important study to show whether the benefit achieved after 12 months on the patch stays stable or hopefully continues to grow with longer duration,” says Kim, who is an investigator in this follow-up trial.
"My son now attends university in Massachusetts, lives on-campus, and eats dorm food. He has so much more freedom," Wong says.
The team is further ahead in the phase 3 follow-up trial for 4-to-11-year-olds. The initial phase 3 trial was not as successful as the trial for kids between one and three. The patch enabled patients to tolerate more peanuts but there was not a significant enough difference compared to the placebo group to be definitive. The follow-up trial showed greater potency. It suggests that the longer patients are on the patch, the stronger its effects.
They’re also testing if making the patch bigger, changing the shape and extending the minimum time it’s worn can improve its benefits in a trial for a new group of 4-to-11 year-olds.
The future
DBV Technologies is using the skin patch to treat cow’s milk allergies in children ages 1 to 17. They’re currently in phase 2 trials.
As for the peanut allergy trials in toddlers, the hope is to see more efficacy soon.
For Wong’s son who took part in the earlier phase 2 trial for 4-to-11-year-olds, the patch has transformed his life.
“My son continues to maintain his peanut tolerance and is not affected by peanut dust in the air or cross-contact,” Wong says. ”He attends university in Massachusetts, lives on-campus, and eats dorm food. He still carries an EpiPen but has so much more freedom than before his clinical trial. We will always be grateful.”
A New Test Aims to Objectively Measure Pain. It Could Help Legitimate Sufferers Access the Meds They Need.
"That throbbing you feel for the first minute after a door slams on your finger."
This is how Central Florida resident Bridgett Willkie describes the attacks of pain caused by her sickle cell anemia – a genetic blood disorder in which a patient's red blood cells become shaped like sickles and get stuck in blood vessels, thereby obstructing the flow of blood and oxygen.
"I found myself being labeled as an addict and I never was."
Willkie's lifelong battle with the condition has led to avascular necrosis in both of her shoulders, hips, knees and ankles. This means that her bone tissue is dying due to insufficient blood supply (sickle cell anemia is among the medical conditions that can decrease blood flow to one's bones).
"That adds to the pain significantly," she says. "Every time my heart beats, it hurts. And the pain moves. It follows the path of circulation. I liken it to a traffic jam in my veins."
For more than a decade, she received prescriptions for Oxycontin. Then, four years ago, her hematologist – who had been her doctor for 18 years – suffered a fatal heart attack. She says her longtime doctor's replacement lacked experience treating sickle cell patients and was uncomfortable writing her a prescription for opioids. What's more, this new doctor wanted to place her in a drug rehab facility.
"Because I refused to go, he stopped writing my scripts," she says. The ensuing three months were spent at home, detoxing. She describes the pain as unbearable. "Sometimes I just wanted to die."
One of the effects of the opioid epidemic is that many legitimate pain patients have seen their opioids significantly reduced or downright discontinued because of their doctors' fears of over-prescribing addictive medications.
"I found myself being labeled as an addict and I never was...Being treated like a drug-seeking patient is degrading and humiliating," says Willkie, who adds that when she is at the hospital, "it's exhausting arguing with the doctors...You dread them making their rounds because every day they come in talking about weaning you off your meds."
Situations such as these are fraught with tension between patients and doctors, who must remain wary about the risk of over-prescribing powerful and addictive medications. Adding to the complexity is that it can be very difficult to reliably assess a patient's level of physical pain.
However, this difficulty may soon decline, as Indiana University School of Medicine researchers, led by Dr. Alexander B. Niculescu, have reportedly devised a way to objectively assess physical pain by analyzing biomarkers in a patient's blood sample. The results of a study involving more than 300 participants were published earlier this year in the journal Molecular Psychiatry.
Niculescu – who is both a professor of psychiatry and medical neuroscience at the IU School of Medicine – explains that, when someone is in severe physical pain, a blood sample will show biomarkers related to intracellular adhesion and cell-signaling mechanisms. He adds that some of these biomarkers "have prior convergent evidence from animal or human studies for involvement in pain."
Aside from reliably measuring pain severity, Niculescu says blood biomarkers can measure the degree of one's response to treatment and also assess the risk of future recurrences of pain. He believes this new method's greatest benefit, however, might be the ability to identify a number of non-opioid medications that a particular patient is likely to respond to, based on his or her biomarker profile.
Clearly, such a method could be a gamechanger for pain patients and the professionals who treat them. As of yet, health workers have been forced to make crucial decisions based on their clinical impressions of patients; such impressions are invariably subjective. A method that enables people to prove the extent of their pain could remove the stigma that many legitimate pain patients face when seeking to obtain their needed medicine. It would also improve their chances of receiving sufficient treatment.
Niculescu says it's "theoretically possible" that there are some conditions which, despite being severe, might not reveal themselves through his testing method. But he also says that, "even if the same molecular markers that are involved in the pain process are not reflected in the blood, there are other indirect markers that should reflect the distress."
Niculescu expects his testing method will be available to the medical community at large within one to three years.
Willkie says she would welcome a reliable pain assessment method. Well-aware that she is not alone in her plight, she has more than 500 Facebook friends with sickle cell disease, and she says that "all of their opioid meds have been restricted or cut" as a result of the opioid crisis. Some now feel compelled to find their opioids "on the streets." She says she personally has never obtained opioids this way. Instead, she relies on marijuana to mitigate her pain.
Niculescu expects his testing method will be available to the medical community at large within one to three years: "It takes a while for things to translate from a lab setting to a commercial testing arena."
In the meantime, for Willkie and other patients, "we have to convince doctors and nurses that we're in pain."
In different countries' national dietary guidelines, red meats (beef, pork, and lamb) are often confined to a very small corner. Swedish officials, for example, advise the population to "eat less red and processed meat". Experts in Greece recommend consuming no more than four servings of red meat — not per week, but per month.
"Humans 100% rely on the microbes to digest this food."
Yet somehow, the matter is far from settled. Quibbles over the scientific evidence emerge on a regular basis — as in a recent BMJ article titled, "No need to cut red meat, say new guidelines." News headlines lately have declared that limiting red meat may be "bad advice," while carnivore diet enthusiasts boast about the weight loss and good health they've achieved on an all-meat diet. The wildly successful plant-based burgers? To them, a gimmick. The burger wars are on.
Nutrition science would seem the best place to look for answers on the health effects of specific foods. And on one hand, the science is rather clear: in large populations, people who eat more red meat tend to have more health problems, including cardiovascular disease, colorectal cancer, and other conditions. But this sort of correlational evidence fails to settle the matter once and for all; many who look closely at these studies cite methodological shortcomings and a low certainty of evidence.
Some scientists, meanwhile, are trying to cut through the noise by increasing their focus on the mechanisms: exactly how red meat is digested and the step-by-step of how this affects human health. And curiously, as these lines of evidence emerge, several of them center around gut microbes as active participants in red meat's ultimate effects on human health.
Dr. Stanley Hazen, researcher and medical director of preventive cardiology at Cleveland Clinic, was one of the first to zero in on gut microorganisms as possible contributors to the health effects of red meat. In looking for chemical compounds in the blood that could predict the future development of cardiovascular disease, his lab identified a molecule called trimethylamine-N-oxide (TMAO). Little by little, he and his colleagues began to gather both human and animal evidence that TMAO played a role in causing heart disease.
Naturally, they tried to figure out where the TMAO came from. Hazen says, "We found that animal products, and especially red meat, were a dietary source that, [along with] gut microbes, would generate this product that leads to heart disease development." They observed that the gut microbes were essential for making TMAO out of dietary compounds (like red meat) that contained its precursor, trimethylamine (TMA).
So in linking red meat to cardiovascular disease through TMAO, the surprising conclusion, says Hazen, was that, "Without a doubt, [the microbes] are the most important aspect of the whole pathway."
"I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
Other researchers have taken an interest in different red-meat-associated health problems, like colorectal cancer and the inflammation that accompanies it. This was the mechanistic link tackled by the lab of professor Karsten Zengler of the UC San Diego Departments of Pediatrics and Bioengineering—and it also led straight back to the gut microbes.
Zengler and colleagues recently published a paper in Nature Microbiology that focused on the effects of a red meat carbohydrate (or sugar) called Neu5Gc.
He explains, "If you eat animal proteins in your diet… the bound sugars in your diet are cleaved off in your gut and they get recycled. Your own cells will not recognize between the foreign sugars and your own sugars, because they look almost identical." The unsuspecting human cells then take up these foreign sugars — spurring antibody production and creating inflammation.
Zengler showed, however, that gut bacteria use enzymes to cleave off the sugar during digestion, stopping the inflammation and rendering the sugar harmless. "There's no enzyme in the human body that can cleave this [sugar] off. Humans 100% rely on the microbes to digest this food," he says.
Both researchers are quick to caution that the health effects of diet are complex. Other work indicates, for example, that while intake of red meat can affect TMAO levels, so can intake of fish and seafood. But these new lines of evidence could help explain why some people, ironically, seem to be in perfect health despite eating a lot of red meat: their ideal frequency of meat consumption may depend on their existing community of gut microbes.
"It helps explain what accounts for inter-person variability," Hazen says.
These emerging mechanisms reinforce overall why it's prudent to limit red meat, just as the nutritional guidelines advised in the first place. But both Hazen and Zengler predict that interventions to buffer the effects of too many ribeyes may be just around the corner.
Zengler says, "Our idea is that you basically can help your own digestive system detoxify these inflammatory compounds in meat, if you continue eating red meat or you want to eat a high amount of red meat." A possibly strategy, he says, is to use specific pre- or probiotics to cultivate an inflammation-reducing gut microbial community.
Hazen foresees the emergence of drugs that act not on the human, but on the human's gut microorganisms. "I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
He adds, "It's a matter of 'stay tuned', I think."