World news – AU – blocking two immune molecules can prevent asthma attacks: a study


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The La Jolla Institute of Immunology (LJI) has found a new study, revealing the key to preventing asthma attacks by blocking two immune molecules at the same time. It is the key to preventing asthma attacks in a mouse model..

Asthma has become a concern for Americans. Ten Americans die every day from this attack. Researchers have discovered a new method that could provide relief to all asthma patients.

“We’ve found a way to prevent the acute inflammatory response to asthma – and we’ve seen a robust and long-term reduction in asthma exacerbations,” says Michael Croft, PhD, professor at LJI and lead author of the new study, published Nov.5, 2020, in the journal Allergy and Clinical Immunology.

When an allergy sufferer encounters an asthma trigger, harmful T cells increase their numbers in the lungs and release particles that cause inflammation.. The new study shows how to throw a wrench in the process.

For the study, Croft Lab focused on blocking OX40L and CD30L, which indicate proteins similar to tumor necrosis factor (TNF), a target protein for many FDA-approved drugs. . These molecules are regulated by allergens and can activate harmful, inflammatory T cells in asthma.

In the new study, Croft and colleagues worked on a mouse model sensitive to house dust mites – a very common allergen and asthma trigger.. Scientists have shown that blocking OX40L and CD30L at the same time can stop the expansion and buildup of harmful T cells in the lungs during an allergen attack, and this then leads to less inflammation.. .

“Combining the output of the two sets of signals allowed a significant reduction in the number of pathogenic T cells, while neutralizing either had a relatively mild effect,” says Croft. This was a very important finding.

Importantly, blocking both OX40L and CD30L also reduced the number of pathogenic T cells that remained in the lungs after an asthma attack.. These « memory » T cells usually trigger inflammation when a person encounters the allergen again. Without OX40L and CD30L in action, very few of these harmful T cells were stuck in the lungs, and the mice had a weaker response to the house dust mite for weeks after the initial treatment.. « This indicates that we have been impairing the immune memory of the allergen, » says Croft..

This study comes after several years of an ineffective clinical trial targeting OX40L. Previous research by Croft Lab and other researchers had suggested that blocking the signals from OX40L could reduce airway inflammation, however antibodies neutralizing against OX40L had no beneficial effect on asthma patients with house dust mites or cat allergies.. . « Why did I fail? » Croft asks. The new study supports the idea that banning the OX40L was not enough.

The research sheds light on the complexity of the immune system and suggests that long-term treatment of inflammatory and autoimmune diseases may require a multi-pronged targeting approach, especially when trying to limit the number of disease-causing T cells that are the central drivers of these diseases..

It will be difficult to test a combination therapy to block both molecules (researchers will need to demonstrate the safety of blocking both separately), but Croft believes that either a dual antibody or a « dual-specific » reagent could block both OX40L and CD30L signals in the treatment One.

Croft is now thinking about the next steps for his lab. Blocking the OX40L and CD30L reduced memory T cells but did not eliminate them all. Croft thinks additional target molecules could be present. « We’re trying to understand what those molecules are, » says Croft..

Asthma, Immunology and Inflammation, La Jolla Immunology Institute

World News – AU – Blocking two immune molecules that can prevent asthma attacks: study
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blocking two immune molecules that can prevent attacks Asthma: A Study


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