New Peanut Therapy Alters DNA 

A new experimental therapy creates changes in the DNA expression of peanut allergy sufferers. 

Using blood tests and DNA sequencing technology, researchers at Stanford University were able to successfully predict which subjects with peanut allergies would react to a peanut test.

Using blood tests and DNA sequencing technology, researchers at Stanford University were able to successfully predict which subjects with peanut allergies would react to a peanut test.

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In the not too distant future, kids with peanut allergies may be able to chomp into sandwiches, candy bars and cookies without their parents fretting that their throats might close up, thanks to new experimental research which has found concrete differences in the DNA of people allergic to peanuts.

At the moment, the best advice doctors can give to those who suffer from peanut allergies is avoid peanuts and carry an epi-pen. But researchers have made amazing strides using new technologies to better understand peanut allergies and how to treat them.

"The biggest impact of this study is that we were looking for mechanisms, and we found them at the DNA level. Now the next question is how sustained are they at the DNA level and whether they can be passed on," says senior author Kari Nadeau, a physician scientist at Stanford University, who is also an allergist and immunologist.

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Using blood tests and DNA sequencing technology, researchers at Stanford University were able to successfully predict which subjects with peanut allergies would react to a peanut test and which had grown tolerant after more than two years of an experimental therapy that exposed subjects to the very source of their allergies. The answer lay in a protein nicknamed FOXP3.

Researchers at Stanford University divided their peanut-allergic subjects, into two groups: one group of 23 subjects was given a nearly invisible speck of peanut flour mixed in with food, usually apple sauce, while a second group of 20 subjects was told simply to avoid peanuts.

Everyday the subjects in the experimental group would eat just a speck of flour. And every two weeks, their dose would increase by 25 percent. Both groups would return to the lab every three months where researchers would assess their reactivity to peanuts in a protected environment. After two years, those who were successfully treated could tolerate 4000mg of protein, about half a tablespoon of peanut flour.

Patients wanted to know whether they would have to continue to eat peanuts everyday for the rest of their lives if they wanted to stave off an allergic reaction, so researchers and Stanford looked for an answer. They stopped patients from taking their daily dose of peanut flour for three months then tested their blood and sequenced their DNA. At 27 months, seven patients passed the challenge and showed no "detectable allergic reaction" to a peanut test. But after another three months of withdrawal from treatment – at 30 months into the trial – only three subjects continued to have a strong immune response.

The determining factor, says Nadeau, was the effectiveness of certain T-cells, a type of white blood cells known as "peacekeepers" because they suppress other "bad actors" – the cells that trigger allergic reactions.

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Researchers next wanted to understand why allergic people's T-cells are weaker than others. They found their answer by looking at their subjects DNA at a very specific type of protein using a groundbreaking new type of research called epigenetics and a certain gene called FOXP3.

"FOXP3 is a marker in our body that can help us with decreasing allergic reaction," says Nadeau.

"Kids who are born without it actually have horrible allergies and autoimmune disease. Most all people have FOXP3 but the question is how is it modulated," she added later.

Epigenetics looks at tiny globs of genetic material, that scientists used to think were junk. Now we know that this extra DNA is not junk and actually changes how our DNA is expressed. Sometimes these globs cause the DNA to produce proteins and sometimes they stop the DNA from producing proteins. But in the case of people with peanut allergies, this extra layer of DNA is harmful. Getting rid of these globs, these chemical modifications actually improve T-cell function so that the body can fight allergic reaction.

At the end of 24 months, all of the subjects who had undergone the peanut treatment showed no allergic response. Their DNA looked similar to a non-allergic person's. But after stopping their daily treatment for a period of three months, the allergic reaction returned for some subjects. By looking at a very specific part of the DNA a gene called FOXP3 inside the very specific T-cells they could predict which subjects would have an allergic response by identifying the people who had regained this extra layer of DNA.

What's more, if the DNA changes are sustainable, it is possible that those who overcome their allergies could pass their immunity onto their kids.

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What this means for future research is that scientists now know where to look to determine whether patients have successfully overcome their allergy or whether they need to continue therapy. And while eating peanuts everyday, especially peanut butter cups, might seem fun at first, people could get bored after a while and stop, says Nadeau.

"This study is impactful because it offers scientist a prototype by which you can look at mechanism and really dig deep because of the tools that we have now have. Tools that wouldn't have been available five years ago," says Nadeau. This therapy does not yet have FDA approval and more research is needed to validate the results of the study.

"You would never want to do this therapy at home because it's something that has to be done in a hospital setting because it's investigational and experimental," says Nadeau.

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