New Approach Slows or Stops Allergic Reactions

In a new experimental approach to treating allergic diseases, scientists have found that cross-linking two genetically engineered receptor molecules in mice can short-circuit the type of allergic reaction that leads to asthma, allergic rhinitis, and even the potentially deadly anaphylaxis caused by food allergy. Their research was reported in the May 2002 issue of Nature Medicine.

The scientists designed and created a molecule called GE2 that acts on two types of immune system cells central to allergic reactions: mast cells and basophils. In people
with allergies, these cells respond to harmless substances like pollen or peanut proteins by releasing chemicals such as histamine that trigger the symptoms of allergic reactions. Histamine, for example, causes swelling, sneezing, itching, and irritation.

GE2 binds to receptor molecules on mast cells and basophils that control the release of histamine. One of these receptor molecules is like a gas pedal: it makes the
allergic reaction go. The other receptor molecule is like a brake, explains senior author Andrew Saxon, M.D., director of the Asthma, Allergy, and Immunologic Disease
Center at the University of California at Los Angeles (UCLA; USA). "However, in this case, the brake only works when coupled with the gas pedal. Therefore, we constructed GE2 so that one end 'steps on' the brake while the other end
binds to the gas pedal. This cross-linking slows or stops the allergic reaction.

In laboratory tests on human mast cells and basophils, the higher the dose of GE2, the less histamine the cells released when stimulated by an allergen. In tests on mice,
GE2 significantly reduced allergic skin reactions. However, many more lab and animal studies will be necessary before this approach can be tested in humans.

The GE2 molecule is called a fusion protein because its two active parts are connected, or fused, by a linking section. As it is constructed now, GE2 contains generic active parts
that indiscriminately block reactions to any allergen, Dr. Saxon says. However, a fusion protein like GE2 could be designed to contain a specific allergen such as a peanut
protein and thereby block only allergic reactions to peanut. If used in allergy injections, these allergen-specific proteins could allow patients to receive higher doses that would be more effective but lack the risk of a dangerous allergic reaction. The study was supported by the US National Institute of Allergy and Infectious Diseases (NIAID).