The study, called PRECISIONS (for Prospective tReatment EffiCacy in IPF uSIng genOtype for Nac Selection), is being funded by a $22 million grant from the National Institutes of Health and Three Lakes Partners, a philanthropic organization dedicated to pulmonary fibrosis care and research.
PRECISIONS has three primary goals. First, it aims to determine whether N-Acetyl-cysteine (NAC) is an effective treatment for individuals with IPF who have a particular variant of the gene TOLLIP, known to play a role in lung immunity.
NAC is an antioxidant, and it has been suggested in can lessen lung damage in IPF, although its efficacy is far from clear, with studies finding conflicting results. Previous research suggested that this may be because NAC is only effective in individuals with particular genotypes. Specifically, the variant TOLLIP rs3750920 T/T, which is present in around a quarter of people with IPF, is associated with better clinical responses to NAC. PRECISIONS aims to directly test this association.
The second goal of PRECISIONS is to develop blood-based assays to help distinguish IPF from other lung diseases with similar symptoms. This will be accomplished by using unbiased analyses of transcriptomics (which genes are ‘off’ and ‘on’ in cells), proteomics (global analysis of proteins in the blood), and other large-scale molecular analyses, in order to identify molecular signatures that are linked with IPF. Such biomarkers could help in predicting an individual’s disease course and response to therapy.
PRECISIONS’ third and final goal is to identify genetic variants that influence an individual’s risk of developing IPF, which may prove useful in monitoring people at a high risk of the disease.
“This innovative study highlights the value of a partnership between a broad range of investigators, the PFF, a philanthropic organization (Three Lakes Partners), and the National Heart, Lung, and Blood Institute (NHLBI). Most importantly, it seeks to provide patients with interstitial lung disease (ILD) access to personalized medicine in which the right medication is used for the right patient,” Fernando Martinez, MD, one of the researchers leading the project, said in a press release.
The project will rely on the PFF Patient Registry and Biorepository, which have collected clinical data and biological samples from over 2,000 pulmonary fibrosis patients.
“The PFF Patient Registry will serve as an invaluable tool to facilitate more efficient enrollment into the NAC pragmatic trial, and to further define the genetic risk factors influencing the development and potential progression of the disease,” said Gregory Cosgrove, MD, chief medical officer at PFF. “It will hopefully allow for the identification of important biomarkers to assist in the diagnosis and care of patients with PF.”
Added Imre North, MD, a co-principal investigator on the project: “PRECISIONS has the potential to really change the scientific landscape over how we view IPF and ILDs by providing molecular classifications while determining if a pharmacogenetically driven treatment can change outcomes.”