Targeting ATP Receptor P2RX4 for Pulmonary Fibrosis
Abstract
Objectives of the Proposed Work: Lung fibrosis is a serious, life-threatening chronic disease of the lung that leads to loss of lung function and ultimately need for lung transplant. Without transplant, which itself has a limited survival potential, lung fibrosis has a survival of only 3 years, and options for medical therapy are limited. None of the current FDA-approved therapies achieve a cure. Our investigative team has assembled compelling preliminary data about the role of macrophages in lung fibrosis. Specifically, for the first time to our knowledge, our preliminary data implicate macrophage secretion of the small molecule adenosine triphosphate (ATP) in the development of fibrosis. Our overall objective is to test, in preclinical mouse models and with human lung samples, the viability of this pathway as a therapeutic target. Types of Patients Benefiting from This Work: Lung fibrosis is increasing in prevalence and is associated with aging. The challenge of lung fibrosis is that there is still no cure, and patients often need a lung transplant. This project will lead to insights into a new pathway that is a potential target for therapeutic drug development. New therapies are urgently needed for active Service Members and Veterans, as well as members of the public at large who suffer with this severe and life-threatening disease. The work proposed would benefit all patients who develop lung fibrosis, including Veterans, active military personnel, and also members of the general population. Furthermore, the clinical study proposed to determine whether there is an association between blood cells called monocytes with clinical outcomes in Veterans with idiopathic pulmonary fibrosis (IPF) is of direct benefit to Veterans. Potential Clinical Applications and Risks: The proposed experiments are highly focused because they will directly examine the viability of specific molecules as therapeutic targets for lung fibrosis. The investigative team has shown in preliminary data with mice that these targets should regulate the fibrotic process, and the experimental plan includes approaches that will directly test their role. Furthermore, our clinical study in Veterans should lead to validation of a novel blood biomarker (monocytes) that would be useful in clinical practice. Timeline to Achieve Patient-related Outcomes: The patient-related outcomes in this proposal are from animal models, human cell-based experiments, and clinical data in our VA study. The results of the lab-based experiments could motivate early phase trials in humans within five years from now. The results of the clinical study will yield results about patient-related outcomes within the first year and throughout the 4 years of the award. How the Research Will Benefit Service Members, Veterans, or their Family Members: This research is of direct benefit to active Service Members. Lung fibrosis is commonly seen in active Service Members as well as Veterans, and it is increasing in prevalence. Our goal is to investigate the ATP pathway as a possible new treatment. Our clinical study on IPF outcomes related to peripheral blood monocytes will benefit Veterans immediately, as the data will establish whether monocytes can be a useful biomarker in the Veteran population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110417
Entities
People
- Mallar Bhattacharya
Organizations
- United States Army
- University of California, San Francisco