Fresh understanding of what causes asthma opens door for new treatment

 

Cardiff University's Professor Daniela Riccardi says that if human trials of a drug to treat asthma are successful, a cure could be on the horizon (Photo: Cardiff University) Sufferers of asthma live with a constant unease that an attack can strike at any time. Equally disconcerting is our lack of understanding of its causes and where a cure might come from. But researchers at Cardiff University may have just lifted the veil on this condition, claiming to have not only uncovered its root cause, but drugs that can curtail its symptoms. In their research, the scientists worked with mouse models and human airway tissue from both sufferers and non-sufferers of asthma. They were able to identify the exact cells that narrow the airways and set off an attack. The team established that environmental triggers like allergens and cigarette smoke activate a receptor known as the calcium sensing receptor (CaSR). It found this in turn to be the driver of asthma symptoms that make breathing difficult. But the good news doesn't stop there. They say CaSR can be neutralized with existing drugs called calcilytics, first produced around 15 years ago as a treatment candidate for osteoporosis. "Our paper shows how these triggers release chemicals that activate CaSR in airway tissue and drive asthma symptoms like airway twitchiness, inflammation, and narrowing," says principal investigator Professor Daniela Riccardi. "Using calcilytics, nebulized directly into the lungs, we show that it is possible to deactivate CaSR and prevent all of these symptoms." For many sufferers of asthma, its symptoms can be kept under control through inhalers and medicine. But around five percent don't respond too well to available treatments, and it is for this minority that this breakthrough could have a huge impact. The team is now shifting its focus to facilitating human trials within two years. It is hopeful that successful trials will lead to new forms of treatment and ultimately, the prevention of asthma all together. "If we can prove that calcilytics are safe when administered directly to the lung in people, then in five years we could be in a position to treat patients and potentially stop asthma from happening in the first place," says Riccardi. The research was published in the journal Science Translational Medicine. Source: Cardiff University

Future asthma treatment may target trigger allergens

 

The humble asthma inhaler may be relegated from lifeblood of treatment to a mere backup device if research into allergen delivery inhibitors continues to bear fruit (Photo: Shutterstock) Asthma attacks are terrifying. They feel almost like the world is closing in around you as you wheeze and cough and gasp for breath. And they often strike suddenly, without warning, when an innocuous event stirs up dust or pollen around you. That terror of unexpected attack that we asthmatics feel every day may largely disappear if a novel new research project pans out. Scientists at the Universities of Cambridge, London, and Manchester have gone after the trigger allergens and developed an inhalable powder from a compound that binds to a major dust mite allergen. This powder could lead to a shift in focus for asthma treatment from relief to inhibition. House dust mites are sources of more than 20 allergen groups that trigger asthma. The group 1 family of allergens has an especially potent effect on allergic asthma sufferers. These allergens are released into the body by way of inhaled dust mite fecal pellets that release their contents after impact with the airway mucosa (the lining of the airway wall that leads to the lungs). That kickstarts an immune response that ends with the patient's airways being narrowed and partially clogged, leaving them gasping for air. Traditional asthma medication comes in here. Corticosteroid inhalers, β-agonist bronchodilators, and other steroid or anti-inflammatory drugs used in inhalers and nebulizers relax affected muscles and relieve symptoms so that patients can breathe easily again. But this new approach attempts to cut the allergic reaction off at the pass. The researchers investigated known inhibitors of Der p 1, a cysteine protease (enzymes that break down proteins) in group 1 of the mite allergens that they explain "is used as a surrogate measure of environmental exposure to house dust mites generally." They then took this as a starting point for an experimental, structure-based drug discovery. They identified compounds, described as "allergen delivery inhibitors," that were converted into an inhalable powder. That powder was tested on rats, with encouraging results: the rats' immune responses were significantly dampened by the drug when they were exposed to a variety of allergens. Animal models don't always mimic human responses to asthma drugs, unfortunately, but if further tests succeed, allergen delivery inhibitors could prove a life-changing new approach to treating allergic asthma. Prevention trumps relief of symptoms, and the millions of asthma sufferers with the allergen-triggered variety of the disease may feel that first-hand if the compound flagged for drug development passes evaluation. A paper describing the research was published in the Journal of Medicinal Chemistry. Source: American Chemical Society

Novel approach to treating asthma: Neutralize the trigger

 

Current asthma treatments can alleviate wheezing, coughing and other symptoms felt by millions of Americans every year, but they don't get to the root cause of the condition. Now, for the first time, scientists are reporting a new approach to defeating asthma by targeting the trigger -- the allergen -- before it can spark an attack. They describe their new compound, which they tested on rats, in ACS' Journal of Medicinal Chemistry. Clive Robinson and colleagues explain that to prevent many health problems, the ideal approach to treatment or prevention involves getting to the cause of a condition and targeting it directly. Asthma, which occurs when the immune system goes into overdrive affecting the airway in response to an otherwise harmless substance, has posed a challenge to this model. That's because it can be set off by different allergens or irritants. But recent studies suggest that the picture might not be as complicated as previously thought. Scientists have found that dust mites are one of the most important triggers of allergic asthma. So Robinson's team wanted to find a way to neutralize mite allergens. The researchers identified a compound that binds to a major dust mite allergen and turned it into an inhalable powder. They tested it on rats and found that it significantly dampened the animals' immune response when they were exposed to a variety of allergens. This compound and other similar inhibitors could hail a new direction in asthma treatment, say the researchers. The authors acknowledge funding from the Wellcome Trust. Story Source: The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length. Journal Reference: Gary K. Newton, Trevor R. Perrior, Kerry Jenkins, Meriel R. Major, Rebekah E. Key, Mark R. Stewart, Stuart Firth-Clark, Steven M. Lloyd, Jihui Zhang, Nicola J. Francis-Newton, Jonathan P. Richardson, Jie Chen, Pei Lai, David R. Garrod, Clive Robinson. The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma. Journal of Medicinal Chemistry, 2014; 57 (22): 9447 DOI: 10.1021/jm501102h

Novel home cleaning method to reduce asthma

 

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A team of researchers from the University of South Carolina received two patents for a new method to rid carpets, mattresses and other furniture of harmful allergens and pests that cause asthma.

The patents (Methods and Compositions for Eliminating Allergens and Allergen-Producing Organisms) are the work of Michael Matthews, Jian Zhang and Allan Quick and uses carbon dioxide (CO₂) to "freeze clean" home fabrics. The process deactivates proteins found in pet dander and can remove smoke residue and other allergy-causing substances. The freezing process also kills dust mites embedded in carpets and mattresses, which feed off human skin particles and are a major cause of asthma.

The researchers are currently perfecting the application method, which utilizes CO2 vapor sprayed directly on fabric. The vapor cools on expansion to form tiny micro-pellets of dry ice that are quickly vacuumed up and the result is completely dry fabric free of allergy-causing agents. Early tests suggest a single cleaning treatment lasts approximately six months and does no harm to the fabric.

The work is funded with multiple external grants, including two from the National Institutes of Health.

About 7 million children, more than 9 percent of the entire child population in the U.S., suffer from asthma, according to the Centers for Disease Control. Asthma rates are even higher for minority and low-income children and asthma attacks also are responsible for 1.8 million emergency room visits each year.

Matthews, a professor of chemical engineering at USC's College of Engineering and Computing, said the method could eventually be ordered by physicians as an effective intervention for children with asthma.

"Our original concept, both in research and in our startup, was to commercialize carbon dioxide technology for medical sterilization," Matthews said. "However, we realized that there was a critical national need to address the removal of asthma triggers from the home. These triggers, which are actually proteins produced by pets and pests, can be removed with our technology."

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Story Source:

The above story is based on materials provided by University of South Carolina. Note: Materials may be edited for content and length.

Albuterol–dosage and side effects.

 

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