New Target Discovered for Non-Type 2 Inflammation in Severe Asthma

Genentech researchers identify oncostatin M as a protein that may be responsible for the severe airway inflammation seen in patients with noneosinophilic asthma.

Severe asthma is categorized based on patients’ response to treatment and the presence of biomarkers, such as immunoglobulin E (IgE), eosinophils, and neutrophils. Allergic asthma, eosinophilic asthma, and non-eosinophilic asthma are types of severe asthma. Patients with allergic asthma typically have high levels of IgE when exposed to allergens. People with eosinophilic asthma have increased eosinophil levels, and those with noneosinophilic asthma show neither increased IgE nor eosinophil levels. But they may have high neutrophil levels.

The presence or absence of these biomarkers has made targeted treatment possible for certain types of severe asthma but elusive for others. Biologics that target cytokines directly involved in IgE or eosinophil activity are helpful in treating allergic asthma and eosinophilic asthma. These agents, however, fail to address the treatment needs of patients with non-eosinophilic asthma. In fact, there exists a scarcity of treatment for this type of asthma.

Noneosinophilic asthma, also called non-type 2 inflammation, does not respond to treatment with inhaled corticosteroids or most biologics FDA-approved to treat other types of severe asthma. Scientists know that bacterial exposure can trigger lung inflammation characteristic of non-eosinophilic asthma but have struggled to understand the link between the two.

Senior scientific researcher Dr. Sarah Headland and colleagues at Genentech Immunology Discovery have discovered a protein that may help solve the puzzle. In research published in Science Translational Medicine in January of this year, Headland and colleagues identified oncostatin M as a protein responsible for the severe airway inflammation seen in patients with noneosinophilic asthma.

The researchers compared airway biopsies from patients with severe asthma, mild to moderate asthma, and individuals without asthma. They found that patients with severe asthma had uncommonly high oncostatin M activity compared to those in the other two groups. The researchers also found that bacterial cell wall component lipopolysaccharide induces oncostatin M activity in patients with non-eosinophilic asthma.

These findings may be promising in terms of developing treatment specific for non-type 2 inflammation in severe asthma. Using the results from this research, South San Francisco-based Genentech is developing a monoclonal antibody to potentially block oncostatin M and prevent airway inflammation in this type of asthma. Experiments have been limited to animal models, but the company intends to create a product for testing in human clinical trials. In collaboration with Novartis, Genentech also developed Xolair (omalizumab), an anti-IgE antibody FDA-approved to treat moderate to severe allergic asthma in adults and children 6 years or older.