A molecule designed to block cat allergies successfully prevented allergic reactions in laboratory mice, as well as in human cells in a test tube, University of California, Los Angeles (UCLA) researchers report in the April issue of Nature Medicine, available online now. In the future, the investigators say, these promising results could lead to a new therapy not only for human cat allergies, but also possibly for severe food allergies such as those to peanuts.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded the research. “This novel approach to treating cat allergies is encouraging news for millions of cat-allergic Americans. Moreover, these results provide proof-of-concept for using this approach to develop therapies to prevent deadly food allergy reactions as well,” says NIAID Director Anthony S. Fauci, M.D.
The injectable treatment puts a brake on the release of a key chemical from cells involved in cat allergy reactions. That chemical, histamine, brings on allergy symptoms such as sneezing, wheezing, itching, watery eyes, and sometimes asthma. When a cat-allergic person touches or inhales a protein found in cat saliva or dander (small scales from its skin or hair), key immune system cells respond by spewing out histamine. Allergy experts estimate that 14 percent of children 6 to 19 years old are allergic to cats.
The treatment comprises a molecule that loosely tethers a feline and a human protein together. The feline end is the notorious protein (called Fel d1) found in cat dander and saliva that causes so much misery in allergy sufferers. On the other end sits a piece of human antibody (called IgG Fcg1) that docks to a cell receptor that can be recruited to stop allergic reactions.
The investigators named the chimeric molecule GFD, or gamma Feline domesticus, for its human and feline parts, explains principal investigator Andrew Saxon, M.D., of UCLA. The cat allergen end of GFD binds to antibodies on the surface of the cell. The human end of GFD links to a different cell surface protein (called FcgRIIB) that interrupts the allergic response.
Dr. Saxon and his colleagues first tested GFD in blood donated by people allergic to cats. They cultured blood cells with either GFD or with a purified human antibody as a control. Then they added the cat protein that triggers allergic reactions to all the blood cell cultures.
“We measured more than 90 percent less histamine in the cultures with GFD,” says Dr. Saxon. “Those results suggested that GFD successfully prevented the immune cells from reacting to cat allergen. The next step was to test GFD in mice that we had made allergic to the allergenic protein found in cat saliva and dander.”
The researchers tested GFD in two different types of allergic mice. One set was genetically engineered to have human cat-allergy cell receptors. These mice were “passively allergic” to cats: they would react to cat protein only after the scientists first injected them with human allergic antibodies to cats. When these mice were then injected with cat allergen, GFD blocked the allergic reaction involving the human cell receptors, an indication that it might also work in people.
Scientists made another set of mice allergic to cats by injecting them with cat protein and an immune system booster. These mice became “actively allergic” to cats: their reactions to cat allergen would be comparable to reactions in a cat-allergic person. Scientists injected some of these mice with GFD, and then injected cat allergen into the windpipes of all the mice, including a control group that was not allergic to cats. GFD damped asthma-like and other allergic reactions in the cat-allergic mice: reactions in the mice that received GFD were similar to the control group mice that were not allergic to cats.
The molecule has the potential to prevent allergic reactions long after injections cease, Dr. Saxon says. However, further research and clinical testing would be required before it might be used in humans. He also is interested in applying this approach to develop a preventive treatment for serious food allergies.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
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Reference: D. Zhu et al. A chimeric human-cat fusion protein blocks cat-induced allergy. Nature Medicine DOI: 10.1038/nm1219 (2005).
The above story is based on materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.
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