Pediatric rare lung diseases, including disorders such as childhood interstitial and diffuse lung diseases primary ciliary dyskinesia, and lung involvement in systemic juvenile inflammatory arthritis, are associated with high morbidity and are often life-threatening. These disorders are poorly understood, under-recognized, and have limited evidence-based therapeutic options. Despite significant advances, PRLD research is impeded by a lack of model systems and knowledge of molecular targets, largely due to a poor understanding of the disease pathogenesis.

Sunday’s session “Accelerating Scientific Advancement of Rare Pediatric Lung Diseases” will focus on recent progress toward addressing scientific gaps and barriers in PRLD research. The latest model systems, tools, and technologies accelerating research in this field will be discussed, as well as recent translational advances for these diseases.

According to session moderator Amy L. Firth, PhD, assistant professor of medicine at the University of Southern California, two of the significant advances discussed during the session will cover the ciliary proteome and mutations in pediatric interstitial lung disease.

“Lawrence Ostrowski, PhD, will be presenting on the ciliary proteome and PCD,” she says. “His talk will discuss quantitative analysis of the ciliary proteome and how identification of several previously unknown proteins as major constituents of human airway cilia may lead to advances for our understanding of PCD.”

Cilia are essential to many cellular processes, and although many major axonemal components have been identified and studied, how they interact to form a functional axoneme is not completely understood.

Amy L. Firth, PhD

“Dr. Ostrowski’s research has focused on understanding the protein composition of human airway cilia and has identified over 400 proteins present in cilia,” Dr. Firth says. “Many of these are previously uncharacterized proteins, some with high abundance in cilia.”

Proteomic analysis may be used to identify candidate genes for the disease-causing mutations through identification and characterization of proteins that are missing in cilia from patients with PCD. The Ostrowski lab has focused on characterizing some of these, including highly abundant ERICH3, C1orf87, and CCDC181.

“These studies will significantly advance our understanding of motile cilia and increase our understanding of PCD defects,” Dr. Firth says.

Following Dr. Ostrowksi’s talk, Matthias Griese, MD, will present on adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3) mutations in pediatric interstitial lung disease. He will discuss his most recent work in this area, focusing on the evaluation of therapeutic options for patients with ABCA3 mutations.

ABCA3 is a phospholipid transporter in lung lamellar bodies essential for the assembly of pulmonary surfactant. Mutations in the ABCA3 gene cause respiratory distress syndrome in neonates and interstitial lung disease in children and adults.

“In early 2018, Dr. Griese published work demonstrating that mutant ABCA3 proteins could be rescued by bithiazole correctors C13 and C17,” Dr. Firth says. “The identification of such lead molecules represents a huge step toward pharmacotherapy of ABCA3 misfolding-induced lung disease.”