|Novel Therapy Tested in Mice Could
Chase Away Cat Allergies
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.
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
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.
News releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Reference: D. Zhu et al.
A chimeric human-cat fusion protein blocks cat-induced
allergy. Nature Medicine DOI: 10.1038/nm1219