Proof-of principle study finds imatinib improves symptoms for patients with severe asthma

May 17, 2017

Mast cells, a type of white blood cell, are present in the airways of severe asthmatics even in the face of aggressive treatment, and their presence is associated with key indicators of severe asthma. It has long been thought that these mast cells contribute to the disease and that targeting them may improve symptoms and quality of life for patients with severe asthma. In a new, proof-of-principle study published in the New England Journal of Medicine, researchers from Brigham and Women's Hospital have found that targeting the mast cells with imatinib, a drug used to effectively treat certain forms of cancer, improved airway hyperresponsiveness, a measure of the sensitivity of the airway, and decreased the number of mast cells present in the airway. Treatment also produced a small improvement in airway function.

"By targeting these , we can actually make a difference for our patients with severe asthma," said Elliot Israel, MD, a physician and researcher in the Division of Pulmonary and Critical Care Medicine at BWH and senior author of the paper. "This is an exciting development because patients with severe asthma often have poor disease control even when adhering to our best and most aggressive therapies."

Imatinib (brand name Gleevec), is one of the first precision medicine cancer therapies and is currently used to effectively treat certain forms of cancer that have a specific mutation. It works by targeting the processes responsible for mast cell development, stem cell factor and its receptor, the KIT receptor tyrosine kinase, which are essential for not only normal mast cell development but also their survival. These new results suggest that KIT-dependent processes and mast contribute to the process of severe asthma, and suggest that and drugs that can inhibit mast cell development may be effective therapies for patients with severe asthma who do not respond well to current treatment options.

"This study shows how the investigator community begins to apply knowledge of basic disease pathogenesis to tailor interventions to specific patient populations, which leads to more effective therapy. This is particularly the case for this patient group with a disease that is difficult to treat and that has a high morbidity rate," said James Kiley, Ph.D., director, Division of Lung Diseases, at the National Heart, Lung, and Blood Institute (NHLBI).

In a double-blind, placebo-controlled 24-week trial of 62 participants with poorly-controlled severe asthma, researchers evaluated the impact of imatinib on the change in airway hyperresponsiveness and mast cell presence. Participants in the treatment group received imatinib for six months. Participants underwent a bronchoscopy with airway biopsy at the beginning and the conclusion of the study to assess airway mast cells. Airway responsiveness and were also measured during the study.

Israel and his colleagues report that patients in the treatment group experienced a reduction in airway hyperresponsiveness compared to placebo. Specifically, after three months, responsiveness decreased 50 percent in those treated with imatinib compared to those who received placebo. A similar degree of difference was seen between the groups at six months. Additionally, researchers found that imatinib reduced serum tryptase, a marker of mast cell activation, compared with placebo. Researchers also report that patients in the treatment group experienced a relaxation and opening up of the airways, which was an unexpected observation. Researchers note that patients in the treatment group experienced higher rates of muscle cramps and an abnormally low level of phosphate in the blood.

While the results are preliminary, Israel and colleagues found that imatinib was more effective in patients who had less eosinophils, a type of disease-fighting white blood cell present in high numbers in certain types of severe asthma.

"There are several new drugs for severe asthma that target the more allergic, or eosinophilic, type of severe asthma. If confirmed, our finding - that targeting mast cells is effective for patients who do not have eosinophilic-type - is particularly exciting because this group of patients, which make up about 40 percent of with , have no current treatment options to control their disease."

Researchers note that larger-scale studies are needed to confirm their finding and evaluate longer durations of therapy in order to definitively determine clinical efficacy. Planning for these trials is underway.

Explore further: Why is asthma worse in black patients?

More information: New England Journal of Medicine (2017). DOI: 10.1056/NEJMoa1613125

Related Stories

Why is asthma worse in black patients?

January 10, 2017
African Americans may be less responsive to asthma treatment and more likely to die from the condition, in part, because they have a unique type of airway inflammation, according to a study led by researchers at the University ...

Study brings hope of a new treatment for asthma sufferers

March 1, 2017
Improved treatments for people with severe asthma are a 'step closer' after a research team led by the University of Leicester identified a breakthrough in the cause of airway narrowing.

A breath of fresh air for severe asthma research

March 10, 2017
Ten to 15 percent of people with asthma have severe asthma, a form of the disease that is not controlled by current medications. Many of these patients are prescribed increased dosages of corticosteroids, but continue to ...

Benralizumab injections reduce exacerbations in severe, uncontrolled asthma, according to two trials

September 5, 2016
A year's course of benralizumab injections has led to a significant decrease in the frequency of asthma exacerbations - cutting the rate of exacerbations by a third to a half compared with placebo among people with the most ...

New treatment for allergic response targets mast cells

November 21, 2016
Researchers from North Carolina State University and the National Institutes of Health (NIH) have developed a method that stops allergic reactions by removing a key receptor from mast cells and basophils. Their work has implications ...

uPAR elevated in bronchial tissue of asthma patients

September 23, 2016
(HealthDay)—Urokinase plasminogen activator receptor (uPAR) is elevated in patients with asthma, with high uPAR levels linked to severe, non-atopic disease, according to a study published online Sept. 14 in Allergy.

Recommended for you

Asthma researchers test substance from coralberry leaves

September 14, 2017
The coralberry could offer new hope for asthmatics. Researchers at the University of Bonn have extracted an active pharmaceutical ingredient from its leaves to combat asthma, a widespread respiratory disease. In mice, it ...

Respiratory experts urge rethink of 'outdated' asthma categorisation

September 12, 2017
A group of respiratory medicine experts have called for an overhaul of how asthma and other airways diseases are categorised and treated.

New 'biologic' drug may help severe asthma

September 7, 2017
(HealthDay)—A "biologic" drug in development to treat severe asthma reduces the rate of serious attacks by about two-thirds compared to a placebo drug, according to preliminary research findings.

Songbird study shows how estrogen may stop infection-induced brain inflammation

August 31, 2017
The chemical best-known as a female reproductive hormone—estrogen—could help fight off neurodegenerative conditions and diseases in the future. Now, new research by American University neuroscience Professor Colin Saldanha ...

New insights into protein's role in inflammatory response

July 28, 2017
A protein called POP2 inhibits a key inflammatory pathway, calming the body's inflammatory response before it can become destructive, Northwestern Medicine scientists have demonstrated in mouse models.

Targeting 'broken' metabolism in immune cells reduces inflammatory disease

July 12, 2017
The team, led by researchers at Imperial College London, Queen Mary University of London and Ergon Pharmaceuticals, believes the approach could offer new hope in the treatment of inflammatory conditions like arthritis, autoimmune ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.