bronchodilators
Can worm drugs open airways via TMEM16A?
Open access · cc by · source: Europe PMC
A >500k-compound screen found niclosamide and nitazoxanide are potent TMEM16A antagonists that fully bronchodilate airways and resist pathways that blunt β-agonists.
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Can worm drugs open airways via TMEM16A?
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~40% of patients exhibit poor β-agonist responsiveness in severe asthma framing.
There is an unmet need in severe asthma where approximately 40% of patients exhibit poor β-agonist responsiveness, suffer daily symptoms and show frequent exacerbations.
Authors screened a library of over half a million compounds.
To identify additional TMEM16A antagonists and characterize their potential as novel bronchodilators, we screened a library of over half a million compounds.
Key findings
~40% of severe asthma patients respond poorly to β-agonists. Niclosamide and nitazoxanide blocked TMEM16A and provided robust bronchodilation, offering a complementary mechanism for poorly controlled asthma/COPD.
Methodology
Screened over half a million compounds for TMEM16A antagonism, characterized niclosamide/nitazoxanide pharmacology, and tested bronchodilation in mouse tracheal rings and human small airways under harsh contractile/inflammatory conditions.
Limitations
In vitro/ex vivo potency is not the same as proven clinical asthma benefit; safety/dosing for inhaled or systemic airway use needs dedicated trials.
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