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Research on a Roll

From the Spring 2010 special edition on the Future of Allergies.

What’s in the pipeline for food allergy treatments.

Idea: Peanut Allergy Vaccine

What’s Involved: The treatment is based on immunotherapy – that is, by slowly introducing the immune system to something it is allergic to, the system will eventually learn to tolerate the allergen. The problem is, with food allergy, anaphylaxis can occur.

To eliminate that risk, researchers have altered a peanut to “trick” the immune system. Dr. Scott Sicherer, an associate professor of pediatrics at the Mount Sinai School of Medicine in New York and a researcher at the school’s Jaffe Food Allergy Institute, explains the concept. He likens the changed peanut to a baby bracelet that spells the word “Peanut”.

“If you altered that bracelet a little bit, let’s say you changed the ‘A’ in peanut to a ‘D’, then it would say PEDNUT instead of PEANUT,” he says. His theory is that the allergic person’s immune system won’t recognize “pednut” and therefore will be less likely to mount an allergic reaction to it. Over time, if it sees “pednut” enough, the immune system might also learn to accept “peanut”. He does not yet know how often the treatment would need to be taken to make this happen.

Where We Stand: Researchers have developed the optimal “altered peanut” and the vaccine has, in fact, reversed peanut allergy in mice. They’ve also determined that the vaccine is best taken rectally, as a suppository. Along with the altered peanut, the vaccine contains heat-killed E. coli bacteria, to signal the immune system that it should react to a bacteria, rather than an allergen.

Now, teams at Mount Sinai and at Johns Hopkins Children’s Center in Baltimore have started a Phase 1 clinical trial with a small group of people to ensure the vaccine is safe. If all goes well, the researchers will move on to Phase 2 studies, which will determine if the vaccine actually helps to reduce peanut allergy in humans.

Idea: Herbal Formula for Food Allergy

What’s Involved: Dr. Xiu-Min Li has been toiling in her lab at the Mount Sinai School of Medicine for years, trying to zero in on the perfect concoction of Chinese herbs that can increase a person’s threshhold for allergenic foods.

She and her colleagues have tested the formula, which includes dried ginger root, processed plums, Chinese peppers and ginseng, extensively in mice. After they stopped the treatment, the mice still did not react to their former allergen six months later. Li hopes the herbal remedy will allow people to come in accidental contact with their allergens and not have a serious reaction.

Where We Stand: Li has tested the treatment in humans and concluded the formula called FAHF-2 is safe and well-tolerated. She also found that people who took FAHF-2 tablets for six months had a reduction of basophil blood cell activity, which suggests a reduction in a person’s allergic tendency.

Now, the work ahead is to prove the treatment is effective, and to determine how much and how often a person should take it. Li was set to begin a Phase 2 study in March in which patients will take FAHF-2 or a placebo for several months. At the moment, this entails taking 24 tablets a day, but Li is working on reducing that number. The theory is that the effect of the treatment will last some time after the person stops taking the tablets.

Li’s goal is to develop a drug that can be taken by prescription, but she says that once the formula is proven effective, she could begin marketing it as a dietary supplement in the U.S. and Canada, perhaps as early as next year, while she continues to get drug approval.

Idea: Oral Immunotherapy or Desensitization

What’s Involved: In this experimental food allergy treatment, doctors give allergic patients increasingly larger doses of their allergen, starting with tiny amounts, to teach their immune systems to build up tolerance to it.

Allergists Dr. Wesley Burks and Dr. Stacie Jones are running numerous trials of oral immunotherapy (OIT) in Arkansas and North Carolina. Most (but not all) children have been able to build up a tolerance to allergens like peanuts, eggs and milk.

Where We Stand: Burks and Jones continue to research the intricacies of OIT, including who should and shouldn’t try it. They’ve found the most common side effects include runny nose, itchy skin, mild wheezing, or abdominal symptoms. They also found that children react to their daily peanut dose less than 5 per cent of the time, but the reactions that do occur are unpredictable. However, it was discovered that more reactions will occur if a child has a viral infection and more if he or she eats the food on an empty stomach. Trials at other centres are also taking place.

In Canada, Dr. Susan Waserman of McMaster University and Dr. Wade Watson of Dalhousie University have secured a grant from the research network AllerGen to start up a small Canadian trial of peanut oral immunotherapy in Hamilton and Halifax. The study will enroll patients 6 years of age and older. In each city, five patients in a “low-dose” group will work their way up to a fraction of a peanut a day, and 10 higher-dose patients will aim to eat the equivalent of 10 peanuts a day. (There will also be a peanut-allergic control group.)

Investigators will draw blood and give patients an oral challenge every three months in order to pin down the stage at which desensitization truly begins. Waserman hopes to begin recruiting patients this spring. Burks suggests that having a desensitization protocol in place that can be widely used by allergists is still several years away.

Idea: Test for Anaphylaxis

What’s Involved: The theory is that levels of a molecule in the blood called platelet-activating factor (PAF) and the enzyme that destroys it – platelet-activating factor acetylhydrolase (PAF-AH) – can help allergists to predict the severity of an individual’s reactions to peanuts, and possibly other allergens. PAF is what researchers term “a bad guy,” bringing on anaphylaxis symptoms such as airway inflammation and dropping blood pressure. Early results of research led by Dr. Peter Vadas, director of allergy and immunology at Toronto’s St. Michael’s Hospital, suggest the possibility of blood tests for these two biological markers, and possibly others. Test findings would help to identify those who face the higher risk of anaphylaxis, enabling physicians to reinforce with such patients the importance of allergy precautions, auto-injectors and a plan for an emergency.

Where We Stand: Vadas and his colleagues have now teased out another marker of anaphylaxis risk. They found people with a history of serious reactions had peanut-specific IgE (the antibody that recognizes peanut as an invader in the allergic) at high levels in the blood along with low levels of PAF-AH. These results haven’t been published yet, and any test using this knowledge still hinges on verification by independent researchers. So Vadas finds it difficult to predict when patients will be offered his test in the allergist’s office.

While it’s also possible this team could develop a drug that interferes with PAF to halt anaphylaxis, testing such a drug is proving problematic. That’s because to study its effectiveness, doctors would have to administer the drug during an anaphylactic reaction, instead of epinephrine, and that could put lives at risk. It’s more likely a drug would be used as a long-term, preventative treatment for allergies, says Vadas, adding that such a study could take years.

Idea: Hypoallergenic Peanut

What’s Involved: Developing a genetically engineered hypoallergenic peanut has been Dr. Hortense Dodo’s goal for at least 10 years. In 2005, she announced she had eliminated the major allergen, Ara h2, using a process called RNA interference technology. Meanwhile, in 2007, Dr. Mohamed Ahmedna made headlines when North Carolina Agricultural and Technical State University announced that the researcher had developed a process which renders peanuts non-allergenic following harvest.

Where We Stand: In the past few years Dodo has managed to silence two other major allergenic peanut proteins, Ara h1 and Ara h3, and likely two minor allergens. She hopes to one day “gradually replace part of the peanut market,” with products clearly labeled to show they were made with hypo-allergenic peanuts. Then, if someone was to ingest the peanut accidentally, there would be less risk of a severe reaction. But, Dodo cautions there is still a lot of testing and regulatory approval that needs to take place before her peanuts show up on the shelves of grocery stores.
Ahmedna is set to begin testing his peanuts, which are treated with a process that changes the structure of the proteins, in humans, using skin-prick and other tests to see if there is a significant decrease in allergenicity. Like Dodo, he hopes his peanuts will be used by commercial manufacturers in the future.

There are concerns in the allergy community, however, about the practical application of hypoallergenic peanuts. “There is huge potential for confusion if both allergenic and hypoallergenic peanuts begin circulating,” says Toronto allergist Dr. Peter Vadas. “How could a kid in a school lunchroom tell the difference between hypoallergenic peanut butter smeared on a table and the real thing?”

First published in Allergic Living magazine.
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