Tough Nut Is Cracked: Antibody treatment stifles peanut reactions

Nathan Seppa

Researchers have successfully demonstrated the first preventive treatment against peanut allergy. The drug, which raises the threshold at which allergic people react to peanuts, could reach the market in 2 to 3 years, the scientists say.

In some ways, a peanut allergy is the worst kind, says Hugh A. Sampson of Mount Sinai School of Medicine in New York. Peanuts and peanut oil crop up in unlikely foods, such as egg rolls and chili, and can trigger severe reactions. Roughly 50 to 100 deaths every year in the United States can be traced to peanut allergies, Sampson says. What's more, while many children outgrow allergies to other foods, he says, "most people don't outgrow a peanut allergy."

Sampson and his colleagues enrolled 84 people who had a peanut allergy. The scientists gave the participants, ages 12 to 60, four injections over 4 months. One-fourth received inert shots; the others got various doses of an experimental antiallergy drug called TNX-901. Neither the researchers nor the volunteers knew which shots were placebos.

Two to 4 weeks after the last injection, the volunteers were brought into a clinic and, at 40-minute intervals, given capsules containing peanut flour. Each person received increasing doses of the flour until researchers diagnosed an allergic reaction.

The test showed that volunteers getting a placebo could withstand the equivalent of only half a peanut before reacting. People who received light doses of TNX-901 could handle slightly more. Study participants getting the highest doses of the drug withstood, on average, the equivalent of about nine peanuts before having a reaction, says study coauthor Donald Y.M. Leung of the National Jewish Medical and Research Center in Denver. Some managed the equivalent of 24 peanuts, he says. He and Sampson estimate that the average accidental exposure to peanuts is equal to one to two peanuts.

The study appears in the March 13 New England Journal of Medicine.

Allergic reactions occur when immune cells respond to a harmless substance by making a rogue version of an otherwise useful type of antibody called immunoglobulin E (IgE). When this wayward antibody binds to so-called mast cells in the skin, the lung, and mucus membranes, those cells produce rash-causing histamines and spur an influx of inflammatory proteins that causes swelling. Such an allergic reaction can bring on anaphylactic shock.

TNX-901 is a genetically engineered antibody that latches onto the rogue IgE antibodies and prevents them from binding to mast cells, Leung says. In the study, people getting TNX-901 showed a significant drop in IgE antibodies in their blood.

Noting that the study applies earlier research on hay fever and asthma to the realm of food allergies, Henry Metzger of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., calls the work an example of "beautiful translational research."

In the same journal issue carrying these findings, researchers in Britain report that baby lotion containing peanut oil may cause peanut allergy in some children (see http://www.sciencenews.org/articles/20030315/food.asp).

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References:

Leung, D.Y.M., H.A. Sampson, et al. 2003. Effect of anti-IgE therapy in patients with peanut allergy. New England Journal of Medicine 348(March 13):986–993. Abstract available at http://content.nejm.org/cgi/content/abstract/348/11/986.

Further Readings:

Chang, T.W. 2000. Pharmacological basis of anti-IgE therapy. Nature Biotechnology 18(February):157–162. Abstract available at http://dx.doi.org/10.1038/72601.

Helmuth, L. 1999. Allergy vaccine may take fear out of nuts. Science News 155(April 3):213. References and sources available at http://www.sciencenews.org/pages/sn_arc99/4_3_99/fob4ref.htm.

Long, A. 2002. The nuts and bolts of peanut allergy. New England Journal of Medicine 346(April 25):1320–1322.

Metzger, H. 2003. Two approaches to peanut allergy. New England Journal of Medicine 348(March 13):1046–1048.

Miyajima, I., et al. 1997. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gamma RIII: Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgF1-dependent passive anaphylaxis. Journal of Clinical Investigation 99(March 1):901–914. Available at http://www.jci.org/cgi/content/full/99/5/901.

Moffatt, M.F., and W.O.C. Cookson. 1999. Gene therapy for peanut allergy. Nature Medicine 5(April):380–381.

Raloff, J. 1996. Peanut allergy found common and increasing. Science News 150(Sept. 7):150.

______. 2003. Unexpected sources of peanut allergy. Science News Online (March 15). Available at http://www.sciencenews.org/articles/20030315/food.asp.

Roy, K. … and K.W. Leong. 1999. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature Medicine 5(April):387–391. Abstract available at http://dx.doi.org/10.1038/7385.

Sampson, H.A. 2002. Peanut allergy. New England Journal of Medicine 346(April 25):1294–1299.

Sources:

Donald Y.M. Leung
National Jewish Medical and Research Center
1400 Jackson Street
Denver, CO 80206

Henry Metzger
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 10, Room 9N228
National Institutes of Health
Mailstop Code 1820
Bethesda, MD 30892-1820

Hugh A. Sampson
Department of Pediatrics
Box 1198
Mount Sinai School of Medicine
1 Gustave L. Levy Place
New York, NY 10029-6574

From Science News, Volume 163, No. 11, March 15, 2003, p. 163.