B4PF1.0 and B4PF2.0

Three Lakes 12-20 is driven to develop therapies that will prevent and ultimately cure PF. To do this, it is essential to study the contributing factors of the disease as early as possible, ideally before patients develop symptoms and prior to significant organ dysfunction.

Understanding what triggers disease initiation and how disease progresses at both the molecular and radiological level will reveal novel biomarkers and drug targets that can be exploited to generate safe effective therapies.

People who have first degree relatives with pulmonary fibrosis have an increased risk of developing PF. To understand the natural progression of “subclinical” or early disease, asymptomatic relative of pulmonary fibrosis patients were evaluated and followed.

Clinical history, blood samples, pulmonary function tests, and HRCTs were collected. At the initial visit, some of the participants underwent a lung biopsy. Follow-up visits were conducted until the participant received a clinical diagnosis of familial pulmonary fibrosis (FPF). The data and samples will be used to understand the drivers of early disease and the factors that contribute to disease progression. 

In the B4PF1.0 project, funding from Three Lakes Foundation was used to analyze lung biopsy samples from patients with a family history of ILD using state-of the art genomic technologies, including single cell sequencing and spatial transcriptomics. The principal investigator of these studies is Jonathan Kropski, MD, Professor of Medicine and Cell and Developmental Biology and the Rudy W. Jacobson Chair in Pulmonary Medicine at Vanderbilt University Medical Center. Nicholas Banovich, PhD, Associate Professor at the Translational Genomics Research Institute (TGen) is a co-investigator.

B4PF1.0 press release from Three Lakes Foundation

This study catalyzed the field to focus on early disease mechanisms and the possibility of early intervention. In addition, the results of these studies contributed to a successful bid for three collaborative grants worth over $20 million to further study molecular drivers and progression of PF.

https://www.tgen.org/news/tgen-s-nicholas-banovich-ph-d-secures-over-8-2-million-in-nih-grants-for-pulmonary-disease-research/

In the B4PF2.0 project, HRCT scans from patients with early disease and from relatives of pulmonary fibrosis patients are being analyzed to identify a radiomic signature for disease risk and progression. Developing a CT-based screening and predictive approach will enable identification of individuals at-risk for progressive pulmonary fibrosis to facilitate other biomarker studies, mechanistic investigations, and cohort enrichment for clinical trials, ultimately leading to safe effective therapies and even a cure.

This project was initiated and announced in 2022.

In partnership with Radiomics, a thorough review of potential imaging partners was conducted which led to the selection of Fluidda, the world leader in Functional Respiratory Imaging, as a collaborator. https://www.fluidda.com/. The

academic leaders of this project are Dr. Jonathan Kropski, and Dr. Anna Podolanczuk, Assistant Professor of Medicine at Weill Cornell Medical College.

Related Publications:

“Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and

mesenchymal lineages in pulmonary fibrosis” published in Sci. Adv. Reference

“Progressive Early Interstitial Lung Abnormalities in Persons at Risk for Familial

Pulmonary Fibrosis: A Prospective Cohort Study” published in Am. J. Respir. Crit. Care Med. Reference

“Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis” published in Nature Genetics. Reference