Latest Allergic Asthma Treatment Could Change the Game

For many years, studies and treatments for allergic asthma have mostly targeted the inflammatory cytokines in the body that react to allergens and produce mucus overproduction, wheezing, and difficulty breathing. Commonly given medications such as omalizumab, dupilumab, mepolizumab, and reslizumab reduce or block the numerous cytokines and antibodies responsible for the asthmatic response, however they only act after the patient’s airway inflammation has progressed.

Dr. Tigno-Aranjuez was looking for a new way to prevent allergen receptors from reacting in the first place. So she applied LRC-TriCEPS, a technique that finds receptors in cells, to a common allergen, the home dust mite. The technology revealed a cell protein called LMAN1 that had previously been unknown to play a role in the body’s allergy response.

Her research was recently published in Cell Reports.

“When we first had this discovery, we wanted to know, ‘What is this protein? What is already known about LMAN1 as an allergen receptor?’ and the interesting thing was that people had not been paying much attention to this protein in the context of allergy or allergic asthma,” she said.

LMAN1 was previously known as a cargo receptor—a protein that transports other proteins inside and outside the cell. Dr. Tigno-Aranjuez, on the other hand, revealed that house dust mite allergens and LMAN1 can bind together on the cell surface to generate an inflammatory or allergic response. Her research also revealed that the binding was dependent on certain mannose sugar structures on the allergens of house dust mites. Because many other common allergens, such as pollen and fungus, are mannosylated, or changed by the addition of mannose sugars, this discovery has enormous potential.

“Our thinking is that this could potentially not just be restricted to dust mites because many other allergens are mannosylated; this could be a very broad receptor that recognizes many different allergens,” she explained. “If you are thinking in terms of potential therapy, by understanding how LMAN1 recognizes dust mites and the consequences of such recognition, you could apply this to many other settings, and that is what we are currently trying to explore.”

Dr. Tigno-Aranjuez’s LMAN1 research is being conducted in conjunction with the Cleveland Clinic. This study’s co-investigator is Dr. Bin Zhang, Associate Professor at the Lerner Research Institute. Dr. Zhang is regarded as an LMAN1 expert.

“LMAN 1 has been largely known as a protein that is involved in transporting proteins from inside cells to the outside of cells,” explained Dr. Zhang. “This research is the first one to show an entirely new function of LMAN1, as a receptor to bring proteins, such as allergens, from outside of cells to the inside. This could open up a new pathway for treatment.”

With hundreds of thousands of allergic asthma cases in the United States each year, and many more globally, this research represents a significant step toward assisting these people.

“Asthma is so prevalent that sometimes, people think, ‘We’ve already got a lot of treatments, we’ve got it covered.’ The reality is that we could always use more options, we could always improve upon existing treatments.” Said Dr. Tigno-Aranjuez. “Many treatments can only be prescribed if you meet certain clinical criteria, many treatments are cost-prohibitive, many are not covered by insurance. So any new treatment we can put forth that could potentially be a more universal treatment would always be an advance.”

Dr. Tigno-Aranjuez and her colleagues are now conducting research to corroborate their theory that LMAN1 recognizes other mannosylated allergens, such as pollen. If confirmed, this could have far-reaching ramifications for future allergy medicines.

Dr. Tigno-Aranjuez emigrated from the Philippines to the United States to pursue graduate and postdoctoral studies at Case Western University in Cleveland. She joined UCF in 2015 and studies immunological signaling pathways in chronic inflammatory disorders such as asthma and Crohn’s disease.

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