Home Health Experimental drugs suppressed peanut allergy in vitro

Experimental drugs suppressed peanut allergy in vitro

Deak et al. / Proceedings of the National Academy of Sciences, 2019


Scientists have developed drugs that, in one experiment, suppressed a peanut allergy reaction: covalent, heterobivalent inhibitors that irreversibly only bind antibodies against the allergenic proteins of the nut, Ara h 2 and
Araah 6. The authors believe that their research will help to develop a cure for peanut allergy. Article published in
the magazine Proceedings of the National Academy of Sciences.

Peanut allergy is one of the eight most common
food allergies. In the US, according to surveys, 1.4 percent of children and 0.6 percent of adults suffer from it. According to a Russian study, in children from 7-10 years old,
living in the Tomsk region, the prevalence of peanut allergy is 0.08 percent (data for Russia as a whole are not freely available). An immediate type of reaction that occurs with food
allergies, allergens are associated with their specific antibodies (sIgE), fixed on the membranes of mast cells. This causes a mechanism that leads to the release of biologically active substances that are responsible for the manifestation of allergies.

Currently there is only one medicine
can block an allergic reaction at the level of allergen binding to antibodies –
omalizumab, which belongs to the class of monoclonal antibodies. It suppresses all immunoglobulins E by binding their surface receptors. Omalizumab demonstrated
efficacy in asthma, but not approved for the treatment of peanut allergy. Moreover
there is a risk that its random effect may lead to unwanted immunosuppression. Such a problem could be the development of
sIgE inhibitors.

It is known,
that the immune system responds most intensively to two peanut proteins, Ara h
2 and Ara h 6. Described multiple sites (epitopes)
of these proteins able to bind to antibodies, but the degree of importance of each of them
them in the development of allergies has not been investigated. The development of target therapy, the target
where all this will be must be preceded by the determination of the allergen epitopes that play the most important role, or immunodominant epitopes.

A group of scientists led by Peter Dick (Peter E. Deak)
from the University of Notre Dame has developed covalent heterobivalent sIgE inhibitors
irreversibly bind to specific antibodies against peanut proteins and inhibit the development of an allergic reaction
in laboratory experiments.

The definition of immunodominant epitopes, scientists have called the most difficult phase of the work. To identify them, they used their more
early development platform
based on nano allergies. They synthesized the nano-allergens that represented
various lipid epitopes of Ara-h proteins
2 and Ara h 6. In addition, the authors conducted a series of studies. ex vivo with
sera from 16 patients with peanut allergy to see which epitopes
cause an allergic reaction more actively.

Scientists have identified two immunodominant epitopes that were
common to all study participants. They synthesized those molecules
selectively associated with specific to these epitope regions of antibodies. These substances inhibited the reaction in response to the crude extract.
peanuts with an efficiency of 80 percent in experiments with serum samples 14 of 16
patients. The authors write that they are most surprised by the fact that there are only two
inhibitor, which only works on two epitopes, has had such expressiveness
action. Control of the safety of experimental medicines
experiments on mice, scientists explained their potential well
portability.

Patients are allergic to many proteins and epitopes. Allergy suppression by turning off the response to just two of them
suggests that we still know very little about how complex allergens are
interaction with antibodies, scientists say. They believe that their preclinical data show
the prospect of further study of sIgE inhibitors as potential drugs to improve prognosis
peanut allergy and other food allergies. The duration of action of such drugs can last for months after they bind to antibodies.

According to scientists, their work speaks for the fact that there are
epitopes, the response of which is most expressive in a large number
allergy sufferers. Antibodies against these epitopes can be directed to therapy that suppresses the immune system
reaction to food allergens. Moreover, the data show that the development of such treatment may not be
require personalization, because some medicines can be suitable for large
sharing people with peanut allergy.

Scientists have previously demonstrated that
Milk allergy has a worse effect on the overall health of children than peanut allergy.
For information on what forms a person's human allergy can take, read the blog "Love."
itching. "

Andrei Ukrainian

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