A team of Inserm researchers from the Cardio-Thoracic Research Centre of Bordeaux (Inserm/University of Bordeaux and Bordeaux University Hospital) has demonstrated the clinical efficacy of gallopamil in 31 patients with severe asthma. This chronic disease is characterised by remodelling of the bronchi, which exacerbates the obstruction of the airways already seen in “classic” asthma. In contrast to the reference treatment, gallopamil has proved capable of reducing the bronchial smooth muscle mass. This work is published in the American Journal of Respiratory and Critical Care Medicine.

Severe asthma is a chronic condition of the airways that affects between 1 and 3% of the world population to a highly variable extent, depending on the country. It is characterised by persistent breathing difficulty, restricted physical activity, frequent nocturnal attacks, and prolonged asthma attacks that require systemic treatment. These symptoms lead to a considerable number of emergency hospital admissions, have a serious impact on the quality of life for patients, and can even result in death.

In severe asthma, bronchial obstruction causes a strong reduction in respiratory capacity. This bronchial obstruction is due to remodelling of the airways, particularly the thickening of the bronchial smooth muscle (BSM) that surrounds them. This phenomenon is associated with a poor prognosis and resistance to even intensive treatment. Until now, no pharmaceutical drug has succeeded in preventing the excessive proliferation of these muscle cells, including corticosteroids, the reference treatment for severe asthma.

In previous work, Patrick Berger and his colleagues had already demonstrated in vitro and ex vivo that this disproportionate growth was triggered by an abnormal entry of calcium into these bronchial smooth muscle cells. In this same article, the scientists had demonstrated in vitro the anti-proliferative effect of gallopamil, which is normally prescribed for certain heart conditions because of its blocking action on calcium channels.

To assess its in vivo efficacy, the researchers then initiated a clinical trial sponsored by Bordeaux University Hospital and supported by the French Ministry and Health and Inserm. For 12 months, they thus measured the effect of the drug on the thickness of the BSM and bronchial wall, and the frequency of asthma attacks in 31 patients.

On analysis, the data showed a significant reduction in BSM in asthmatic patients treated with gallopamil compared with the placebo group. The drug therefore enabled a significant reduction in the thickness of the bronchial wall in patients.

After this phase, both patient groups were monitored for 3 months after stopping treatment. It then became apparent that individuals treated with gallopamil had significantly fewer prolonged attacks than the placebo group.

This pilot study thus provides proof of concept that the calcium channel blocker is able to reduce bronchial remodelling through its action on the smooth muscle cells in individuals suffering from severe asthma.

Other studies involving larger patient cohorts will have to be put in place to confirm these results. Moreover, although gallopamil seems to affect the occurrence of prolonged asthma attacks, Patrick Berger emphasises the need to test gallopamil over a longer treatment period in order to confirm this observation.


New Target.

Researchers have found a potential new target for treating asthma, according to a study led by researchers at the University of Colorado School of Medicine at the Anschutz Medical Campus and published in the journal Nature Communications.

About 10 million Americans and more than 300 million people worldwide have asthma. The most common therapies now used with asthma patients address airway muscle contractions triggered by inflammation, but those treatment results are often temporary or incomplete.

In the article in Nature Communications, Christopher Evans, PhD, associate professor of medicine at the CU School of Medicine, and his co-authors propose targeting other factors related to the overproduction of mucus, an often overlooked factor that causes breathing problems associated with asthma.

Specifically, Evans and his colleagues found that the protein Mucin 5AC (Muc5ac) plays a critical role in airway hyper-reactivity, a characteristic feature of asthma that makes it difficult to breathe. In experiments with mice, the scientists found that genetic removal of Muc5ac eliminated airway hyper-reactivity.

“The role of mucus as a cause of asthma has been misunderstood and largely overlooked,” Evans said. “We found that it is a potential target for reducing obstruction in asthma.”


Researchers in the United Kingdom, the United States, Sweden and Canada report in Nature that they have discovered more than 30 genes that have strong effects on Immunoglobulin E (IgE), allergies and asthma.

IgE is the antibody that triggers allergic responses. Among the genes are promising novel drug targets for treating allergies and asthma. Allergies affect 30 percent of the population and 10 percent of children suffer from asthma.

The researchers also found that the genes are concentrated in eosinophils, a white cell that ignites inflammation in asthmatic airways. The genes indicate when the eosinophils are activated and primed to cause the most damage. The newly found activation signals provide a possible means of directing treatments by predicting who will respond before starting therapy.

David Schwartz, MD, chairman of the Department of Medicine at the University of Colorado School of Medicine at the Anschutz Medical Campus, is one of the team of researchers who contributed to the report, published Feb. 18 in Nature. Ivana Yang, PhD, associate professor of medicine the School of Medicine, also contributed to the report.

The research team used a novel technique to discover these genes, known as an “epigenome wide association study (EWAS).” Epigenetic changes to DNA do not alter the underlying sequence of the genetic code but can still be passed on as cells divide. They program the cells to form specialized types and tissues.

Cell Type.

Scientists led by molecular immunologists at the Keck School of Medicine of the University of Southern California (USC) have identified a way to target a recently discovered cell type that causes asthma, paving the way to cure the chronic respiratory disease that affects 25 million Americans.

The team, which includes investigators from Janssen Research and Development, Dana-Farber Cancer Institute and Harvard Medical School, will publish its results in the March 17 edition of the peer-reviewed scientific journal Immunity.

Asthma is a chronic lung disease that irritates and narrows the airways, according to the Centers for Disease Control and Prevention. With no known cure for the 7 million children who suffer from this disease in the United States, as well as millions of adults, the goal of asthma treatment is to control the symptoms. The exact causes of this chronic disease are unknown, but researchers believe a combination of genetic and environmental factors contribute to developing asthma. Discovered within the last decade, type 2 innate lymphoid cells, or ILC2s, are a subset of immune cells that trigger primary asthma symptoms such as mucus production and hypersensitive airways. ILC2s do not express previously identified immune cell markers, however, making them tough to target.

“If we can target ILC2s, we might be able to cure asthma or exacerbations caused by these particular cells,” said Omid Akbari, Ph.D., associate professor of molecular and cellular immunology at the Keck School of Medicine of USC and principal investigator of the study. “In this study, we discovered molecules critical to ILC2 homeostasis, survival and function. We believe that targeting these molecules or related pathways could one day cure a patient with ILC2-dependent asthma.”

Akbari’s team used mouse and human cells to show that inducible T cell costimulator molecules (ICOS) and their interaction with ICOS-ligand (ICOS-L) are crucial for ILC2 function and survival. ICOS and ICOS-L are proteins that influence cell behavior and cell response. Akbari’s team developed a humanized mouse model to show how human ILC2s function in vivo; the model is currently being used to study how ILC2s contribute to human asthma and test potential therapies in preclinical studies.

“Because ILC2s are the only cells that express both ICOS and ICOS-L, our research sets the stage for designing new therapeutic approaches that target ILC2s to treat asthma,” said Hadi Maazi, D.V.M., Ph.D., a research associate in Akbari’s lab and the study’s first author.


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