By the Blouin News Science & Health staff

A new drug target for asthma treatment

by in Medicine, Research.

An aide for U.S. Sen. Barbara Boxer (D-CA) sets up a photograph of a child with asthma during a press conference.

An aide for U.S. Sen. Barbara Boxer (D-CA) sets up a photograph of a child with asthma during a press conference.

Researchers from University of Iowa have found an enzyme in the lung of asthmatic patients whose hyperactivity triggers their symptoms and can be used as an indicator of the severity of the condition. The study, published in the journal Science Translational Medicine, shows that inhibition of this enzyme, called CaMKII, can protect asthmatic mice and offers a new putative drug target to fight asthma.

Asthma is chronic lung disease which affects the life of 25 million people in the United States alone. Difficulty to breath, coughing and chest tightness are a few of the symptoms, the cause being the narrowing of the airway epithelium and the lining of the inner tubes that carry oxygen. The narrowing of the airway is the result of inflammation triggered by certain agents, called allergens, inhaled by an individual.

There is no cure for asthma yet and sufferers can only alleviate the symptoms, which can be from minor to severe. Asthma can even cause, or contribute to, death. Changes in the lifestyle that will reduce exposure to allergens and medicine, such as steroids, can be used to control the disease.

“It’s a kind of an epidemic without a clear, therapeutic option.” Dr. Mark Anderson, professor of internal medicine and co-leader of the study says.

Asthma sufferers have an increased amount of reactive oxygen species (ROS) in their lungs and their breath compared to healthy individuals. Elevated ROS levels are also observed in heart disease and this is associated with CaMKII, an enzyme which Anderson’s lab is focusing on.

The research team measured and compared the amount of ROS in the lungs of healthy individuals, mild asthmatic patients and patients with severe, untreatable form of asthma. They found that CaMKII is hyper activated in the patients’, but not in the healthy individuals’, lungs. And more importantly, the more severe the condition, the more activated CaMKII was.

This means that CaMKII can be a good indicator of asthma progression. But if CaMKII activation is blocked, what happens? To study this, scientists used mouse models of the disease. When these mice inhale allergens, they present asthma symptoms, such as inflammation, increased size of specific airway cells (goblet cells), mucus production in the airway etc. The researchers found that it was CaMKII that promoted the symptoms in these mice when they sensed ovalbumin and Aspergillus fumigatus, two common allergens. Later, they synthesized a molecule that blocks CaMKII, and as they were expecting, no treated mice presented any asthma symptom when inhaled the allergen.

These mice were protected and the results “suggest that these airway lining cells are really important for asthma, and they’re important because of the oxidative properties of CaMKII,” says Anderson. “This is completely new and could meet a hunger for new asthma treatments. Here may be a new pathway to treat asthma.”

Due to differences between mice and humans in the airway epithelium, further work is now required to prove that the same applies to humans. Scientists must also find out whether CaMKII inhibition will be a good therapeutic strategy for all, or some, subtypes of asthma (e.g. allergic, non-allergic). However, this study not only offers a putative therapeutic strategy for asthma, but also provides invaluable information on other diseases that are associated with ROS and CaMKII activity, such as cardiac diseases and cancer.