Can worm drugs open airways via TMEM16A?
A >500k-compound screen found niclosamide and nitazoxanide are potent TMEM16A antagonists that fully bronchodilate airways and resist pathways that blunt β-agonists.
Source
Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways
What they did
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.
What they found
~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.
The limits
What it doesn't show
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.
Key terms
- TMEM16A
- Calcium-activated chloride channel (CaCC) involved in airway smooth-muscle contraction and mucus biology.
- Niclosamide
- Approved anthelmintic repositioned here as a potent TMEM16A antagonist.
- Nitazoxanide
- Approved antiparasitic likewise identified as a TMEM16A antagonist bronchodilator.
- β-agonist desensitization
- Use- and inflammation-related pathways that blunt β2-agonist bronchodilation.
- Drug repurposing
- Finding new indications for already-approved medicines.
- ASM
- Airway smooth muscle whose excitation-contraction coupling involves TMEM16A.
Flashcards
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
Quiz yourself
Poor β-agonist response is framed as about:
Common questions
What unmet need is cited?
~40% of severe asthma patients show poor β-agonist responsiveness.
Screen scale?
Over half a million compounds.
Key hits?
Niclosamide and nitazoxanide (and related compounds).
Functional airway result?
Robust bronchodilation of mouse tracheal rings and human small airways.