MCC Therapeutics scientists and co-founders recently published a paper titled: “Therapeutic potential of synergistic mucociliary clearance for cystic fibrosis airways by β-adrenergic plus cholinergic agonists” in The Journal of Clinical Investigation (JCI). The paper delineates the findings of a mechanism of action of the drugs formoterol and methacholine in restoring mucus clearance from the airways.
Mucociliary clearance (MCC) plays a pivotal role in host innate defense of the airways. Impaired mucus clearance contributes to cystic fibrosis (CF) and other obstructive airway diseases such as non-cystic fibrosis bronchiectasis (NCFB), chronic obstructive pulmonary disorder (COPD), chronic asthma and primary ciliary dyskinesia (PCD). Although mucus and other airway epithelial secretions play a critical role in protecting the lung during acute injury, impaired mucus clearance after chronic mucus hyperproduction causes airway obstruction and infection, which contributes to morbidity in common obstructive lung disorders.
In the present study we used the clinically approved β-adrenergic agonist formoterol and cholinergic agonist methacholine. Airway apical surface delivery of the agonists was effective in 2 in vivo CF animal models (sheep and rats). The increased mucociliary clearance velocity (MCCV) of a single dose in the sheep model was prolonged for approximately 24 hours. We found that simultaneous application of the 2 agonists speeded MCCV as effectively as sequential application and without airway constriction. When the agonists were combined with highly effective (CFTR) modulator therapy (HEMT) in CF patients derived cells, the agonists caused further increases in MCCV.
The study also reports results of a single ascending dose (SAD) clinical trial in healthy volunteers and patients with CF demonstrating safety and tolerability as well as early efficacy in volume and weight of expectorated mucus. “These results resolve some of the uncertainties regarding the effects in the airway and tolerability of these combined agonists and speak of their great potential to alleviate mucus obstruction.” Said Dr. Carlos Milla, Stanford University and co-founder of MCC Therapeutics. “Since we demonstrated that the synergistic effect of the agonists is effective at restoring MCC in a CFTR independent manner, the combined outcomes of the study provide solid basis for the application of the two drugs in muco-obstructive lung diseases. This even more taking into account that mucus accumulation continues to be an unmet need for these patients and emerging data points to detrimental effects of commonly used drug combinations”.
MCC Therapeutics is planning to launch a Phase 1 single ascending dose, followed by a multiple ascending dose clinical trial in bronchiectasis (NCFB) patients. The trial is planned to start in late 2026.
Forward Looking Statements
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