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.”
The response to the COVID-19 pandemic will soon become the responsibility of President-elect Biden. As is clear to anyone who honestly looks, the past 10+ months of this pandemic have been a disastrous litany of mistakes, wrong actions, and misinformation.
The result has been the deaths of 240,000 Americans, economic collapse, disruption of routine healthcare, and inability of Americans to pursue their values without fear of contracting or spreading a deadly infectious disease. With the looming change in administration, many proposals will be suggested for the path forward.
Indeed, the Biden campaign published their own plan. This plan encompasses many of the actions my colleagues and I in the public health and infectious disease fields have been arguing for since January. Several of these points, I think, bear emphasis and should be aggressively pursued to help the U.S. emerge from the pandemic.
Support More and Faster Tests
When it comes to an infectious disease outbreak the most basic question that must be answered in any response is: "Who is infected and who is not?" Even today this simple question is not easy to answer because testing issues continue to plague us and there are voices who oppose more testing -- as if by not testing, the cases of COVID cease to exist. While testing is worlds better than it was in March – especially for hospital inpatients – it is still a process fraught with unnecessary bureaucracy and delays in the outpatient setting.
Just this past week, friends and colleagues have had to wait days upon days to get a result back, all the while having to self-quarantine pending the result. This not only leaves people in limbo, it discourages people from being tested, and renders contact tracing almost moot. A test that results in several days is almost useless to contact tracers as Bill Gates has forcefully argued.
We need more testing and more actionable rapid turn-around tests. These tests need to be deployed in healthcare facilities and beyond. Ideally, these tests should be made available for individuals to conduct on themselves at home. For some settings, such as at home, rapid antigen tests similar to those used to detect pregnancy will be suitable; for other settings, like at a doctor's office or a hospital, more elaborate PCR tests will still be key. These last have been compromised for several months due to rationing of the reagent supplies necessary to perform the test – an unacceptable state of affairs that cannot continue. Reflecting an understanding of the state of play of testing, the President-elect recently stated: "We need to increase both lab-based diagnostic testing, with results back within 24 hours or less, and faster, cheaper screening tests that you can take right at home or in school."
Roll Out Safe and Effective Vaccine(s)
Biden's plan also identifies the need to "accelerate the development of treatments and vaccines" and indeed Operation Warp Speed has been one solitary bright spot in the darkness of the failed pandemic response. It is this program that facilitated a distribution partnership with Pfizer for 100 million doses of its mRNA vaccine -- whose preliminary, and extremely positive data, was just announced today to great excitement.
Operation Warp Speed needs to be continued so that we can ensure the final development and distribution of the first-generation vaccines and treatments. When a vaccine is available, it will be a Herculean task that will span many months to actually get into the arms (twice as a 2-dose vaccine) of Americans. Vaccination may begin for healthcare workers before a change in administration, but it will continue long into 2021 and possibly longer. Vaccine distribution will be a task that demands a high degree of competence and coordination, especially with the extreme cold storage conditions needed for the vaccines.
Anticipate the Next Pandemic Now
Not only should Operation Warp Speed be supported, it needs to be expanded. For too long pandemic preparedness has been reactive and it is long past time to approach the development of medical countermeasures for pandemic threats in a proactive fashion.
What we do for other national security threats should be the paradigm for infectious disease threats that too often are subject to a mind-boggling cycle of panic and neglect. There are an estimated 200 outbreaks of viral diseases per year. Luckily and because of hard work, for many of them we have tools at our hands to control them, but for the unknown 201st virus outbreak we do not –as we've seen this year. And, the next unknown virus will likely appear soon. A new program must be constructed guaranteeing that we will never again be caught blindsided and flatfooted as we have been with the COVID-19 pandemic.
A new dedicated "Virus 201" strategy, program, and funding must be created to achieve this goal. This initiative should be a specific program focused on unknown threats that emanate from identified classes of pathogens that possess certain pandemic-causing characteristics. For example, such a program could leverage new powerful vaccine platform technologies to begin development on vaccine candidates for a variety of viral families before they emerge as full-fledged threats. Imagine how different our world would be today if this action was taken after SARS in 2003 or even MERS in 2012.
Biden should remove the handcuffs from the Centers for Disease Control and Prevention (CDC) and allow its experts to coordinate the national response and to issue guidance in the manner they were constituted to do without fear of political reprisal.
Resurrect Expertise
One of the most disheartening aspects of the pandemic has been the denigration and outright attacks on experts in infectious disease. Such disgusting attacks were not for any flaws, incompetence, or weakness but for their opposite -- strength and competence – and emanated from a desire to evade the grim reality. Such nihilism must end and indeed the Biden plan contains several crucial remedies, including the restoration of the White House National Security Council Directorate for Global Health Security and Biodefense, a crucial body of experts at the White House that the Trump administration bafflingly eliminated in 2018.
Additionally, Biden should remove the handcuffs from the Centers for Disease Control and Prevention (CDC) and allow its experts to coordinate the national response and to issue guidance in the manner they were constituted to do without fear of political reprisal.
Shore Up Hospital Capacity
For the foreseeable future, as control of the virus slips away in certain parts of the country, hospital capacity will be the paramount concern. Unlike many other industries, the healthcare sector is severely constrained in its ability to expand capacity because of regulatory and financial considerations. Hospital emergency preparedness has never been prioritized and until we can substantially curtail the spread of this virus, hospitals must remain vigilant.
We have seen how suspensions of "elective" procedures led to alarming declines in vital healthcare services that range from childhood immunization to cancer chemotherapy to psychiatric care. This cannot be allowed to happen again. Hospitals will need support in terms of staffing, alternative care sites, and personal protective equipment. Reflecting these concerns, the Biden plan outlines an approach that smartly uses the Departments of Defense and Veterans Affairs assets and medical reserve corps, coupled to the now-flourishing telemedicine innovations, to augment capacity and forestall the need for hospitals to shift to crisis standards of care.
To these five tasks, I would add a long list of subtasks that need to be executed by agencies such as the Centers for Medicare and Medicaid, the Food and Drug Administration, and many other arms of government. But, to me, these are the most crucial.
***
As COVID-19 has demonstrated, new deadly viruses can spread quickly and easily around the globe, causing significant loss of life and economic ruin. With nearly 200 epidemics occurring each year, the next fast-moving, novel infectious disease pandemic could be right around the corner.
The upcoming transition affords the opportunity to implement a new paradigm in pandemic response, biosecurity, and emerging disease response. The United States and President-elect Biden must work hard to to end this pandemic and increase the resilience of the United States to the future infectious disease threats we will surely face.
Dr. Adalja is focused on emerging infectious disease, pandemic preparedness, and biosecurity. He has served on US government panels tasked with developing guidelines for the treatment of plague, botulism, and anthrax in mass casualty settings and the system of care for infectious disease emergencies, and as an external advisor to the New York City Health and Hospital Emergency Management Highly Infectious Disease training program, as well as on a FEMA working group on nuclear disaster recovery. Dr. Adalja is an Associate Editor of the journal Health Security. He was a coeditor of the volume Global Catastrophic Biological Risks, a contributing author for the Handbook of Bioterrorism and Disaster Medicine, the Emergency Medicine CorePendium, Clinical Microbiology Made Ridiculously Simple, UpToDate's section on biological terrorism, and a NATO volume on bioterrorism. He has also published in such journals as the New England Journal of Medicine, the Journal of Infectious Diseases, Clinical Infectious Diseases, Emerging Infectious Diseases, and the Annals of Emergency Medicine. He is a board-certified physician in internal medicine, emergency medicine, infectious diseases, and critical care medicine. Follow him on Twitter: @AmeshAA
Abortions Before Fetal Viability Are Legal: Might Science and the Change on the Supreme Court Undermine That?
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
Viability—the potential for a fetus to survive outside the womb—is a core dividing line in American law. For almost 50 years, the Supreme Court of the United States has struck down laws that ban all or most abortions, ruling that women's constitutional rights include choosing to end pregnancies before the point of viability. Once viability is reached, however, states have a "compelling interest" in protecting fetal life. At that point, states can choose to ban or significantly restrict later-term abortions provided states allow an exception to preserve the life or health of the mother.
This distinction between a fetus that could survive outside its mother's body, albeit with significant medical intervention, and one that could not, is at the heart of the court's landmark 1973 decision in Roe v. Wade. The framework of viability remains central to the country's abortion law today, even as some states have passed laws in the name of protecting women's health that significantly undermine Roe. Over the last 30 years, the Supreme Court has upheld these laws, which have the effect of restricting pre-viability abortion access, imposing mandatory waiting periods, requiring parental consent for minors, and placing restrictions on abortion providers.
Viability has always been a slippery notion on which to pin legal rights.
Today, the Guttmacher Institute reports that more than half of American women live in states whose laws are considered hostile to abortion, largely as a result of these intrusions on pre-viability abortion access. Nevertheless, the viability framework stands: while states can pass pre-viability abortion restrictions that (ostensibly) protect the health of the woman or that strike some kind a balance between women's rights and fetal life, it is only after viability that they can completely favor fetal life over the rights of the woman (with limited exceptions when the woman's life is threatened). As a result, judges have struck down certain states' so-called heartbeat laws, which tried to prohibit abortions after detection of a fetal heartbeat (as early as six weeks of pregnancy). Bans on abortion after 12 or 15 weeks' gestation have also been reversed.
Now, with a new Supreme Court Justice expected to be hostile to abortion rights, advances in the care of preterm babies and ongoing research on artificial wombs suggest that the point of viability is already sooner than many assume and could soon be moved radically earlier in gestation, potentially providing a legal basis for earlier and earlier abortion bans.
Viability has always been a slippery notion on which to pin legal rights. It represents an inherently variable and medically shifting moment in the pregnancy timeline that the Roe majority opinion declined to firmly define, noting instead that "[v]iability is usually placed at about seven months (28 weeks) but may occur earlier, even at 24 weeks." Even in 1977, this definition was an optimistic generalization. Every baby is different, and while some 28-week infants born the year Roe was decided did indeed live into adulthood, most died at or shortly after birth. The prognosis for infants born at 24 weeks was much worse.
Today, a baby born at 28 weeks' gestation can be expected to do much better, largely due to the development of surfactant treatment in the early 1990s to help ease the air into babies' lungs. Now, the majority of 24-week-old babies can survive, and several very premature babies, born just shy of 22 weeks' gestation, have lived into childhood. All this variability raises the question: Should the law take a very optimistic, if largely unrealistic, approach to defining viability and place it at 22 weeks, even though the overall survival rate for those preemies remains less than 10% today? Or should the law recognize that keeping a premature infant alive requires specialist care, meaning that actual viability differs not just pregnancy-to-pregnancy but also by healthcare facility and from country to country? A 24-week premature infant born in a rural area or in a developing nation may not be viable as a practical matter, while one born in a major U.S. city with access to state-of-the-art care has a greater than 70% chance of survival. Just as some extremely premature newborns survive, some full-term babies die before, during, or soon after birth, regardless of whether they have access to advanced medical care.
To be accurate, viability should be understood as pregnancy-specific and should take into account the healthcare resources available to that woman. But state laws can't capture this degree of variability by including gestation limits in their abortion laws. Instead, many draw a somewhat arbitrary line at 22, 24, or 28 weeks' gestation, regardless of the particulars of the pregnancy or the medical resources available in that state.
As variable and resource-dependent as viability is today, science may soon move that point even earlier. Ectogenesis is a term coined in 1923 for the growth of an organism outside the body. Long considered science fiction, this technology has made several key advances in the past few years, with scientists announcing in 2017 that they had successfully gestated premature lamb fetuses in an artificial womb for four weeks. Currently in development for use in human fetuses between 22 and 23 weeks' gestation, this technology will almost certainly seek to push viability earlier in pregnancy.
Ectogenesis and other improvements in managing preterm birth deserve to be celebrated, offering new hope to the parents of very premature infants. But in the U.S., and in other nations whose abortion laws are fixed to viability, these same advances also pose a threat to abortion access. Abortion opponents have long sought to move the cutoff for legal abortions, and it is not hard to imagine a state prohibiting all abortions after 18 or 20 weeks by arguing that medical advances render this stage "the new viability," regardless of whether that level of advanced care is available to women in that state. If ectogenesis advances further, the limit could be moved to keep pace.
The Centers for Disease Control and Prevention reports that over 90% of abortions in America are performed at or before 13 weeks, meaning that in the short term, only a small number women would be affected by shifting viability standards. Yet these women are in difficult situations and deserve care and consideration. Research has shown that women seeking later terminations often did not recognize that they were pregnant or had their dates quite wrong, while others report that they had trouble accessing a termination earlier in pregnancy, were afraid to tell their partner or parents, or only recently received a diagnosis of health problems with the fetus.
Shifts in viability over the past few decades have already affected these women, many of whom report struggling to find a provider willing to perform a termination at 18 or 20 weeks out of concern that the woman may have her dates wrong. Ever-earlier gestational limits would continue this chilling effect, making doctors leery of terminating a pregnancy that might be within 2–4 weeks of each new ban. Some states' existing gestational limits on abortion are also inconsistent with prenatal care, which includes genetic testing between 12 and 20 weeks' gestation, as well as an anatomy scan to check the fetus's organ development performed at approximately 20 weeks. If viability moves earlier, prenatal care will be further undermined.
Perhaps most importantly, earlier and earlier abortion bans are inconsistent with the rights and freedoms on which abortion access is based, including recognition of each woman's individual right to bodily integrity and decision-making authority over her own medical care. Those rights and freedoms become meaningless if abortion bans encroach into the weeks that women need to recognize they are pregnant, assess their options, seek medical advice, and access appropriate care. Fetal viability, with its shifting goalposts, isn't the best framework for abortion protection in light of advancing medical science.
Ideally, whether to have an abortion would be a decision that women make in consultation with their doctors, free of state interference. The vast majority of women already make this decision early in pregnancy; the few who come to the decision later do so because something has gone seriously wrong in their lives or with their pregnancies. If states insist on drawing lines based on historical measures of viability, at 24 or 26 or 28 weeks, they should stick with those gestational limits and admit that they no longer represent actual viability but correspond instead to some form of common morality about when the fetus has a protected, if not absolute, right to life. Women need a reasonable amount of time to make careful and informed decisions about whether to continue their pregnancies precisely because these decisions have a lasting impact on their bodies and their lives. To preserve that time, legislators and the courts should decouple abortion rights from ectogenesis and other advances in the care of extremely premature infants that move the point of viability ever earlier.
[Editor's Note: This article was updated after publication to reflect Amy Coney Barrett's confirmation. To read other articles in this special magazine issue, visit the e-reader version.]