Sep 9 2014
In mice, the answer appears to be "yes," but making sure the same can happen in humans is a task that Fred Finkelman, MD, professor of medicine and pediatrics in the University of Cincinnati's (UC) College of Medicine and a researcher at Cincinnati Children's Hospital Medical Center, is attempting to tackle.
"We have discovered something that works in mice and we want to find out if it will work in people," says Finkelman. "If it works in people we may have a good way to suppress all allergies."
Finkelman, leading a team of researchers at UC and Cincinnati Children's, has received a three-year grant of $734,986 from Food Allergy Research & Education (FARE) to test whether food allergies can be safely suppressed by rapid desensitization with a laboratory grown monoclonal antibody, one that targets and deactivates the cells that play a key role in allergic reactions.
Allergy sufferers, Finkelman explains, make molecules called IgE antibodies, which sit on histamine-filled "mast cells" and are spread throughout the body. When the body is exposed to an allergen, the allergen attaches itself to the IgE on the mast cell, which then "explodes," sending its chemical contents throughout the body and causing the allergic reaction.
Finkelman says that the laboratory-grown monoclonal antibody they will test has already proven to remove both the IgE and the IgE receptors on mast cells in mice, suppressing food allergies. But, he adds, this occurred over a period of weeks and he and his team would like to see it happen even sooner in humans.
"We want it to work overnight," says Finkelman. "We have a strategy for changing the exact part of the molecule our antibody recognizes so that it will work more quickly, much more quickly."
Food allergies affect 15 million Americans and result in some 200,000 emergency department visits per year - a visit every three minutes.
Finkelman will test his theories in two sets of mice-one group that has been given a human receptor for IgE and a second group of mice that actually have human cells embedded in them. Success in these mouse models could eventually lead to clinical trials in humans.
"Since we are using an antibody that binds to a particular receptor and our initial studies were in the mouse, the antibody was specific for the mouse receptor," says Finkelman. "Now we have to go to an antibody that is specific for the human version of the same receptor."
And in order to speed up the allergy suppression, Finkelman and team will use a technique called rapid desensitization, a trick that allergists have long used to treat patients allergic to penicillin, says Finkelman.
"Allergists found years ago that they could get around this [penicillin allergy] by giving you first a tiny dose of penicillin, too small to cause a dangerous reaction or make you feel you bad," says Finkelman. "They discovered that half an hour or an hour later they could give you double that dose, and then half an hour or hour later they could double it again and they could keep on doing this until you received a fully therapeutic dose and now instead of going into shock you are going to do just fine.
"Our process would not cure allergies but it would suppress allergies. It would suppress several different types of allergies, especially, food allergies, skin allergies and maybe, to a lesser extent, hay fever and asthma and it would do it very quickly and would do it very safely. That's our goal.
"This is still science and not engineering. There are things that have to be worked out. We have been working with mice, but there is a difference between the mouse and humans in addition to the size and the tail. Something that is safe and effective in mice might not be safe and effective in people and that's why we need all this extra work," says Finkelman.
Finkelman says that the therapies he's testing are designed to suppress anaphylaxis, a potentially fatal reaction that can occur within minutes of consuming or being exposed to food, drugs or insect stings or bites.
"It doesn't matter what type of food is causing it, but what matters is it is caused by an allergen associated with the antibody IgE," says Finkelman.
"Currently, there is no cure for food allergy, and no FDA-approved therapy that can prevent life-threatening reactions. FARE is committed to funding research that will lead to treatments that protect all individuals with food allergies," said James R. Baker, Jr., MD, Interim CEO at Food Allergy Research & Education (FARE). "We are pleased to support Dr. Finkelman's study, which shows great promise."
Other researchers participating in the study include: Marat Khodoun, PhD, assistant professor in the division of immunology, rheumatology and allergy UC; Suzanne Morris, MD, research associate professor of immunology at UC; Richard Strait, MD, an assistant professor of pediatrics at UC and Cincinnati Children's emergency medicine physician; Durga Krishnamurthy, PhD, postdoctoral fellow in the division of immunology at Cincinnati Children's; Jim Mulloy, PhD, professor of pediatrics at UC and part of the division of experimental hematology at Cincinnati Children's, and Alexey Porollo, assistant professor of pediatrics at UC and faculty member in the UC Department of Environmental Health.
The same team of researchers has also received a four-year $1.3 million grant from the National Institute of Allergy and Infectious Diseases that supports studies of how rapid desensitization with anti-IgE receptor antibody works and its use for prevention of anaphylaxis.
Food Allergy Research & Education (FARE) is a 501(c)(3) nonprofit organization that works on behalf of the 15 million Americans with food allergies, including all those at risk for life-threatening anaphylaxis. This potentially deadly disease affects 1 in 13 children in the United States - or roughly two in every classroom. FARE's mission is to find a cure for food allergies, and to keep individuals with food allergies safe and included.
Source: University of Cincinnati Academic Health Center
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