Protein HMGB1 may be the key to better asthma treatment

A new study, published in the Journal of Allergy and Clinical Immunology, investigates a potential new approach to designing drugs for the treatment of asthma. Better interventions could be on the horizon.

Asthma causes an individual’s airways to become inflamed and narrow, and additional mucus is produced. Breathing becomes difficult for this person, who may wheeze and cough as a result.

An estimated 1 in 12 people in the United States have asthma, which equates to around 25 million people.

Worryingly, the number of individuals with asthma appears to be rising. Between 2001 and 2009, the number of U.S. individuals diagnosed with asthma grew by 4.3 million. In 2007, asthma was linked to 3,447 deaths in the country.

There are a range of potential triggers for asthma. These include pollen, molds, dust mites, animal dander, air pollution, certain medications, and exercise.

Current medications can effectively treat the symptoms for many people but, as the lead author of the current study, Dr. Ruth Sander, says: “For a number of people with asthma, particularly severe asthma, treatment is not 100 percent effective. Although a number of new therapies are under investigation for allergy-related asthma, there is still a need for new therapies for asthma that is not related to allergies.”

The steady rise in asthma cases, its potential to be fatal, and the shortfalls of medication for some individuals, all make asthma research an important field of study.

A recent study, conducted at the University of Leicester in the United Kingdom, investigated the role of a specific protein in asthma called high-mobility group box 1 (HMGB1). The researchers hope that their findings might pave the way to designing more effective treatments.

HMGB1 is a chromatin protein, meaning that it helps to organize DNA and regulate its transcription in the nucleus of cells. It is secreted by immune cells – including monocytes, macrophages, and dendritic cells – and promotes the inflammatory response.

The current study used mucous and muscle tissue from the airways of people with mild to moderate cases of asthma. Smooth muscle in the airways is known to contribute significantly to the symptoms of asthma; it overcontracts, increases in mass, and releases chemicals involved in the inflammation response.

Once analyzed, data from the samples showed that HMGB1 is, as expected, a pivotal factor in the etiology of asthma. Although HMGB1 has been implicated in asthma in earlier studies, these results add a new level of detail.

“We have shown that the amount of HMGB1, a protein that can be released in the airways by cells involved in inflammation or by damaged cells, is increased in the mucous from the airways of people with severe asthma.”

Dr. Ruth Sander, University of Leicester, Department of Infection, Immunity, and Inflammation

Dr. Sanders continues: “To our knowledge, this is the first study to show a direct effect of HMGB1 on enhancing airway muscle contraction in response to stimuli. The findings of this research bring us a step closer to improved treatments for people with severe asthma.”

This is the early phase of studies into this new target pathway, and new pharmaceuticals are a long way down the line. However, it marks an important leap forward; by understanding HMGB1 and its role in asthma, novel interventions can eventually be trialled.