• Posted January 18, 2024

Mouse Study Hints at New, Safe Way to Counter Allergies

Allergic to peanuts? To cats? To pollen?

A new targeted therapy may have the potential to help a person ward off an allergic reaction prompted by the specific source of their allergy, Northwestern University researchers report.

The therapy uses nanoparticles to deactivate mast cells, which are the immune cells responsible for immediate allergic reactions.

In a mouse study, the therapy was 100% successful in preventing allergic responses, according to a report published Jan. 16 in the journal Nature Nanotechnology.

Responding to an allergen, mast cells normally dump biochemicals called histamines into the body.

Histamines in turn prompt an inflammatory response resulting in allergy symptoms -- itchy skin, sneezing, watery eyes and, in extreme cases, anaphylactic shock.

“Currently, there are no methods available to specifically target mast cells,” said lead researcher Evan Scott, a professor of biomedical engineering and immunology at Northwestern.

“All we have are medications like antihistamines to treat symptoms, and those don't prevent allergies. They counteract effects of histamines after the mast cells already have been activated,” Scott added in a university news release. "If we had a way to inactivate the mast cells that respond to specific allergens, then we could stop dangerous immune responses in severe situations like anaphylaxis as well as less serious responses like seasonal allergies.”

Mast cells are best known for causing allergic responses, but it's not practical to shut them all down because they play other important roles in the body, like regulating blood flow and fighting parasites.

“Although some drugs are under development, there are currently no FDA-approved drugs that inhibit, or eliminate, mast cells,” said co-researcher Dr. Bruce Bochner, a Northwestern professor of allergy and immunology. “This has been difficult mainly because drugs that can affect mast cell activation or survival also target cells other than mast cells, and thus tend to have unwanted side effects due to influences on other cells.”

The new nanoparticle technology aims to disable specific, allergy-related mast cells through a two-step process, the researchers explained.

The nanoparticles are coated with antibodies capable of shutting down mast cells, and they also carry an allergen that corresponds to a person's specific allergy. For example, to treat peanut allergy it would contain a peanut protein.

The allergen in the nanoparticle binds to the precise mast cells responsible for a specific allergy. At the same time, the antibodies on the nanoparticle engage with receptors on mast cells that inhibit their response.

“Given these two contradictory signals, the mast cell decides that it shouldn't activate and should leave that allergen alone. It selectively stops a response to a specific allergen,” Scott said. “The beauty of this approach is that it does not require killing or eliminating all the mast cells. And, from a safety standpoint, if the nanoparticle accidentally attaches to the wrong cell type, that cell just won't respond.”

“You can use any allergen that you want, and you will selectively shut down the response to that allergen,” Scott added.

To test this therapy, the researchers developed mice carrying human mast cells in their tissues. They exposed the mice to an allergen and delivered the nanotherapy at the same time.

No mice experienced anaphylactic shock and all survived.

“The simplest way to monitor an allergic response is to track changes in body temperature,” Scott said. “We saw no changes in temperature. There was no response. Also, the mice remained healthy and did not display any outward signs of an allergic reaction.”

Experts note however that animal research doesn't always pan out in humans, so more study is needed.

Researchers next plan to explore their therapy for treating other mast cell-related diseases, including a rare form of mast cell cancer called mastocytosis.

More information

The American Academy of Allergy, Asthma and Immunology has more about mast cell activation.

SOURCE: Northwestern University, news release, Jan. 16, 2024