# New approach to treating allergic diseases



## wanderingstar (Dec 1, 1999)

This was posted on the Co-Cure list. I wonder if it might have implications for food intolerances seen in IBS? MikeNL, you out there?NATIONAL INSTITUTES OF HEALTHNational Institute of Allergy and Infectious DiseasesNIH NEWS RELEASEEMBARGOED FOR RELEASEThursday, April 30, 20025:00 p.m. EDT*EXPERIMENTAL THERAPY STOPS ALLERGIC REACTIONS IN MICE*Scientists supported by the National Institute of Allergyand Infectious Diseases (NIAID) have devised a new,experimental approach to treating allergic diseases. *Inmice, the scientists used a genetically engineered moleculeto connect two receptors on the key immune system cellsthat cause allergic reactions. Cross-linking thesereceptor molecules short-circuited the type of allergicreaction that leads to asthma, allergic rhinitis, and eventhe potentially deadly anaphylaxis caused by food allergy."This work represents an entirely new approach to treatingallergic diseases," says NIAID Director Anthony S. Fauci,M.D. * "The prevalence of allergic disease has increasedsignificantly in recent decades, and there simply are notmany promising therapeutic strategies out there. We hopethat NIAID's continued support of research into themechanisms of allergy will lead to other innovativeconcepts like this one.""This research does what science is supposed to do," saysMarshall Plaut, M.D., chief of NIAID's Allergic MechanismsSection. "The researchers succeeded in translating ascientific observation into a clever therapeutic idea."Details of this work, performed by a team of scientists atthe University of California at Los Angeles (UCLA) and theUniversity of New Mexico, appear in the May issue of"Nature Medicine".The scientists designed and created a molecule called GE2that acts on two types of immune system cells central toallergic reactions: mast cells and basophils. In peoplewith allergies, these cells respond to ordinarily harmlesssubstances, such as pollen or peanut proteins, by releasingchemicals such as histamine that trigger the symptoms ofallergic reactions. Histamine, for example, causesswelling, sneezing, itching, and irritation.GE2 binds to receptor molecules on mast cells and basophilsthat control the release of histamine. "One of thesereceptor molecules is like a gas pedal: it makes theallergic reaction go. The other receptor molecule is like abrake," explains senior author Andrew Saxon, M.D., directorof the UCLA Asthma, Allergy, and Immunologic DiseaseCenter. "However, in this case, the brake only works whencoupled with the gas pedal. Therefore, we constructed GE2so that one end 'steps on' the brake while the other endbinds to the gas pedal. This cross-linking slows or stopsthe allergic reaction."In laboratory tests on human mast cells and basophils, thehigher the dose of GE2, the less histamine the cellsreleased when stimulated by an allergen. In tests on mice,GE2 significantly reduced allergic skin reactions.Although many more lab and animal studies will be necessarybefore this approach can be tested in humans, it has thepotential to treat such diseases as allergic asthma,allergic rhinitis, chronic urticaria (hives), angioedema(hive-like swelling) and even the sometimes deadlyanaphylaxis brought on by allergic reactions to certainfoods such as peanuts, Dr. Saxon says.The GE2 molecule is called a fusion protein because its twoactive parts are connected, or fused, by a linking section.As it is constructed now, GE2 contains generic active partsthat indiscriminately block reactions to any allergen, Dr.Saxon says. However, a fusion protein like GE2 could bedesigned to contain a specific allergen such as a peanutprotein and thereby block only allergic reactions topeanut. These allergen-specific fusion proteins could beused in allergy shots to make them safer and moreeffective: The patient could receive higher doses ofallergen in the shot, making it more effective, withoutrunning the risk of suffering a dangerous allergicreaction, because the "braking end" of the fusion proteinwould stop that reaction.NIAID is a component of the National Institutes of Health(NIH). NIAID supports basic and applied research toprevent, diagnose, and treat infectious and immune-mediatedillnesses, including HIV/AIDS and other sexuallytransmitted diseases, illness from potential agents ofbioterrorism, tuberculosis, malaria, autoimmune disorders,asthma and allergies.Press releases, fact sheets and other NIAID-relatedmaterials are available on the NIAID Web site at http://www.niaid.nih.gov. --------------------------------------------* REFERENCE: D Zhu et al. A novel human Fcy-Fce bifunctionalfusion protein inhibits FceRI-mediated degranulation."Nature Medicine" 8(5):518-21 (2002).*


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