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Breakthrough Drug Discovered For Asthma And COPD Treatment

by Pooja Shete on January 9, 2021 at 1:22 PM
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 Breakthrough Drug Discovered For Asthma And COPD Treatment

Even though progress has been made in managing asthma and chronic obstructive pulmonary disease (COPD), poorly controlled symptoms for these respiratory diseases can lead to severe shortness of breath, hospitalizations or even death.

The study conducted at the University Of South Florida Morsani College Of Medicine is published in the journal ACS Pharmacology and Translational Science.

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Stephen Liggett, MD, vice dean for research at the University of South Florida Morsani College of Medicine and a USF Health professor of medicine, molecular pharmacology and physiology, and biomedical engineering said, "Only about 50 percent of asthmatics, and an even lower percentage of people with COPD, achieve adequate control of lung inflammation and airway constriction with currently available medications. So, we're clearly missing something from our drug armamentarium to help all these patients."

The researchers have discovered various subtypes of bitter taste receptors (TAS2Rs) -- G protein-coupled receptors which are expressed on the human smooth airway muscle cells deep inside the lungs. In case of asthma and COPD, narrowing of the airway decreases the air flow.
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Activation of TAS2Rs resulted in opening of the airway.For the treatment of asthma, COPD and other obstructive lung diseases, the researchers are looking for new drugs that target smooth muscle TAS2Rs to open constricted airways.

Promising Drug Opens Constricted Airway

In the preclinical study, the researchers identified and characterized about 18 new compounds that activate bitter taste receptor subtype TAS2R5 promoting relaxation (dilation) of human airway smooth muscle cells. Among the several drug candidates, 1,10 phenanthroline-5,6-dione (T5-8 for short) was found to be 1,000 times more potent than some of the other compounds tested, and it demonstrated good efficacy in human airway smooth muscle cells grown in the laboratory.

In an earlier screening conducted by another research group, only one compound called T5-1 agonist was found that would bind to and specifically activate the TASR5 bitter taste receptor with limited effectiveness. The researchers used this compound as their starting point and they aimed for a much better drug that can be administered to humans.

The senior author of the study, Dr. Liggett said, "The two key questions we asked were: 'Is it possible to find a more potent agonist that activates this receptor?' and 'Is it feasible to deliver by inhalation given the potencies that we find? T5-8 was the bronchodilator agonist that worked best. There were a few others that were very good as well, so we now have multiple potential new drugs to carry out the next steps."

T5-8 was found superior to all the other bronchodilator agonists screened and it showed a maximum relaxation response (50 percent) substantially greater than that of albuterol (27 percent). Albuterol is prescribed as a rescue inhaler belonging to class of direct bronchodilator (beta-2-agonist) to treat wheezing and shortness of breath due to asthma and COPD. However, this drug or its derivatives is not effective for all patients and its overuse has been linked to increased hospitalizations.

Dr Liggett has stated that have two distinct classes of drug working in different ways to open the airways would be an important step to help patients optimally control their symptoms. He also said that this drug discovery successfully meets the criteria needed to advance the compound toward its first trial as a potential first-in-class bronchodilator targeting airway receptor TAS2R5.

Source: Medindia
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