Introduction ABCA3 transporter deficiency leads to severe interstitial lung disease (ILD). Treatments are limited and lung transplantation is the only option in terminal stages. CFTR modulator therapies have revolutionized the management of cystic fibrosis. The homology between ABCA3 and CFTR (also known as ABCA7) suggests that CFTR modulators could be a therapeutic option in patients with ABCA3 mutations? induced ILD.

Aims To assess the safety and effectiveness of CFTR modulators in patients with ABCA3 deficiency.

Method CFTR modulators were delivered to 3 patients with end-stage respiratory insufficiency associated with ABCA3 compound heterozygous mutation. Two adult patients (pt 1 and 2 aged 30 and 22 years old) received Elexacaftor-Tezacaftor-Ivacaftor (ETI). Pt 3 was a 4-yo child treated with Lumacaftor-Ivacaftor. Patients were assessed at weeks 6 and 12 post treatment?s onset.

Results Parents of pt 3 reported initial cough improvement , but he developed Adenovirus infection at week 3 requiring intensive care unit hospitalization. Treatment was stopped. Pts 1 and 2 reported no side effect and improved dyspnea. Pt1 showed functional improvement at M3 (400 mL gain in forced vital capacity, 30 m gain in 6 minutes walking test distance) and moderate regression of ground glass opacities on CT scan. CT and functional respiratory tests were stable for pt2 but sweat chloride concentration was improved.

Conclusion In this short-term proof-of-concept pilot study, ETI was safe, and showed promising results for ILD adult patients caused by ABCA3 mutations. These results support the need for a multicenter prospective international trial.