The Problem
IPF is linked to the accumulation of senescent, or old, cells in the lung, creating scar tissue (fibrosis) which progressively stiffens them. This disables the patient, eventually suffocating them within 2-4 years. IPF creates a high burden of senescent cells in the lungs, and removing senescent cells powerfully impacts the disease. Previous drug candidates were tested in a problematic model which doesn’t accurately reflect the reality of IPF patients, whose pathology accumulates over many years in lungs that have limited capacity to heal.
The Goal
Develop a new and more reliable model for IPF, using older animals with fibrosis induced over a longer period of time. This will allow any new drug to be tested accurately for real disease modification and their ability to impact real patients.
The Status
This is a new project – founded when other projects needed a more reliable animal model for testing. It will support all research currently being on IPF globally.
Closing the Translation Gap on a Ruinous Disease of Aging
Idiopathic pulmonary fibrosis (IPF) is a disease of aging that has been closely linked to senescent cell accumulation. Patients develop chronic, progressive interstitial fibrosis of the lungs, characterized by progressively-worsening dyspnea and reduction in lung volume as well as reduced lung diffusion capacity. Evidence implicates senescent cells (SEN) in the pathogenesis of the disease. Human patients have a high burden of SEN alveolar epithelial cells and fibroblasts, and senescent cell ablation prevents or reverses animal models of the disease. New senolytic agents therefore hold the potential to be the first disease-modifying therapy for IPF.
A critical caveat to further study is that the animal model of IPF involves instillation of agents that induce inflammation and fibrosis (such as bleomycin or particulates) into the lungs of juvenile mice. Unlike IPF patients, these young animals’ lung epithelia rapidly regenerates, and the condition resolves within 28 days. The aim is to develop a more faithful model for testing small-molecule senolytics and immunotherapies as rejuvenation biotechnologies for IPF using pre-aged animals with lower levels of bleomycin to phenocopy the progressive nature of the disease in an aged organism. This is expected to yield a more faithful model in which successfully-tested rejuvenation biotechnologies will have a high translational potential of impacting patient lives.
Team Members
Please visit the Work With Us page to learn about available positions.
Dr. Amit Sharma
Principal Investigator
Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India. He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.
Dr. Sharma is the SENS Research Foundation Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.
Funding
Annual Budget
145,000 USD
