2026-06-02 スタンフォード大学
Two existing drugs act with surprising synergy to move lung mucus through major airways, an action that could help patients with cystic fibrosis and other respiratory diseases. | Getty Images
◆CFでは遺伝子異常により気道内に粘性の高い粘液が蓄積し、慢性的な感染や肺機能低下を引き起こす。研究では、βアドレナリン受容体作動薬とコリン作動薬を組み合わせることで、単独投与では得られない相乗効果が生じ、動物モデルにおいて気道粘液の輸送・排出能力（粘液線毛クリアランス）が著しく向上した。これは気道表面の水分分泌や線毛運動が協調的に活性化されたためと考えられる。
◆研究チームは、この効果がヒトでも再現されれば、病原体の排除促進や慢性肺感染の抑制につながる可能性があると期待している。両薬剤は既に臨床で使用実績があるため、新薬開発に比べて実用化までの期間短縮も期待される。今後は臨床試験を通じて、安全性と有効性の検証が進められる予定である。
＜関連情報＞
- https://news.stanford.edu/stories/2026/06/drug-combo-potential-cystic-fibrosis
- https://www.jci.org/articles/view/201541
βアドレナリン作動薬とコリン作動薬の併用による嚢胞性線維症気道に対する相乗的な粘液線毛クリアランスの治療可能性 Therapeutic potential of synergistic mucociliary clearance for cystic fibrosis airways by β-adrenergic plus cholinergic agonists
Nam Soo Joo, Susan E. Birket, Johnathan D. Keith, Juan P. Ianowski, Xiaojie Luan, Jacquelyn Spano, Jennifer B. Bollyky, Marissa N. Dobry, Juan R. Sabater, Ryan W. Williams, John F. Engelhardt, Jeffrey J. Wine, and Carlos E. Milla
Journal of Clinical Investigation Published: April 2, 2026
DOI:https://doi.org/10.1172/JCI201541
Abstract
Mucociliary clearance (MCC) is an innate defense mechanism that normally keeps airways clean but is dysfunctional in cystic fibrosis (CF) and other muco-obstructive pulmonary diseases. Previously we discovered that activating adenyl cyclase in combination with a cholinergic agonist increased MCC velocity (MCCV) synergistically in ex vivo WT and CF ferret and WT piglets. For what we believe is the first time, we show in vivo synergistic MCC using FDA approved β-adrenergic and cholinergic drugs delivered to the apical surface of WT and CF rats and a CF sheep model. Also, a single dose of the combined drugs is tolerated by humans. As for mechanisms, via ex vivo experiments, we show the combined agonists increased net fluid secretion mainly by stimulating gland secretion and by inhibiting surface absorption, consequently increasing airway surface liquid depth. They also increased net base secretion and increased ciliary beat frequency. Additional ex vivo and in vitro experiments show that the combined agonists had additive effects when combined with highly effective CF transmembrane conductance regulator modulator therapy. The synergistic increase in MCCV induced by this combination of agonists offers therapeutic potential for treating muco-obstructive pulmonary diseases, including CF.
