Oncostatin M (OSM) Emerges as a Novel Therapeutic Target for Severe Asthma: Genentech Advances OSM-Blocking Antibody Toward Clinical Development

Asthma is a common respiratory disease, with patients exhibiting recurrent symptoms such as wheezing, shortness of breath, chest tightness, or coughing. Although viruses,BacteriaEnvironmental toxins and allergens may trigger asthma exacerbations, butAsthmaThe exact trigger factors and molecular mechanisms remained unclear until now.

Approximately half of asthma patients exhibit type 2 cytokine (IL-4, IL-5, IL-13)-driven inflammation. Most targeted therapies for asthma treat the condition by intervening in these pathways. However, for patients with non-type 2 inflammatory asthma, aside from non-specific treatments such as inhaled corticosteroids and β-adrenergic agonists, there are few available treatment options. Therefore, identifying triggers and therapeutic targets for asthma exacerbations is crucial forAsthmaThe treatment of the patient is very important.

In an article published in Science Translational Medicine, a research team from Genentech discovered that oncostatin M (OSM) is a severeAsthmaThe main driver, using OSM-specific blocking antibodies, can reduce inflammation and mucus production without affecting critical antibacterial pathways and antibacterial immunity in the body.

The respiratory tract of the human body is "home" to a wide variety ofBacteria, which together form a distinctive microbial ecosystem. Moreover, the microbial ecosystem is closely related to an individual's respiratory diseases.AsthmaThe quantity and quality of bacterial components in the respiratory tract of critically ill patients often change, andBacteriaThe secreted components may also lead to the deterioration of the disease.

In order to clarifyBacteriaTriggerAsthmaThe relevant mechanism, researchers fromBacteriaThe main secretions are lipopolysaccharides (LPS), which serve as the starting point for finding answers. The pro-inflammatory molecules mainly induced by LPS include IL-α, IL-β, TNF-α, IL-8, and so on. In addition, there is another cytokine called OSM.

OSM is a member of the gp130 cytokine family, involved in various physiological responses. Elevated OSM concentrations are often observed in allergic diseases, and studies have reported its involvement in arthritis andDiabetesThe anti-inflammatory properties of OSM were discovered in the wound healing model. Is OSM the causeBacteriaWhat is the main "culprit" behind related respiratory inflammation?

Researchers first conducted biopsies and analyses on the airways of healthy volunteers, mild/moderate asthma patients, and severe asthma patients, finding that, compared to the transcriptomes of mild/moderate and healthy controls, those of severeAsthmaThe most significantly elevated regulator in the patient transcriptome is OSM, and this characteristic is associated with the activation of inflammatory and mucus production pathways.

Further mechanistic studies revealed that OSM can trigger extensive responses in primary human airway epithelial and mesenchymal cells, including the induction of cytokine and chemokine axes, increased expression of cytokine and histamine receptors in epithelial and mesenchymal cells, initiation of mucus production programs within airway epithelial cells, as well as goblet cell differentiation and mucus production.

Blocking OSM with an OSM-specific antibody can reduce many of theAsthmaThe relevant pathophysiological characteristics, and it does not affect the key antibacterial pathways and antibacterial immunity in the body. (BioValleyBioon.com）