A study led by Massachusetts General Hospital (MGH) researchers may have found a key mechanism underlying idiopathic pulmonary fibrosis (IPF), a usually fatal lung disease for which transplantation is the only successful treatment.
The investigators found that a specific molecular pathway appears responsible for key aspects of the scarring of lung tissue that characterizes IPF, the cause of which is currently unknown. The results will appear in the January issue of Nature Medicine and have received early online release.
“Identifying the key role of this pathway in the development of fibrosis gives us an exciting new target for devising treatments,” says Andrew Tager, MD, of the MGH Pulmonary and Critical Care Unit, who led the study. “An agent that blocks this pathway is already being developed as a potential cancer treatment, and we're hoping to be able to test it in our animal model of IPF to determine whether it might be a candidate for trials in patients.”
About 50,000 new cases of IPF are diagnosed in the U.S. each year, primarily in people aged 50 to 75. While some patients may survive for extended periods, in others the diseases progresses rapidly, leading to death in an average of 3 to 5 years. Theories about the cause of IPF previously focused on chronic inflammation of the lungs, but recent evidence has suggested that an abnormal healing response to some sort of lung injury may be responsible.
The primary characteristic of IPF is scarring (fibrosis) of the lung surface, rendering it unable to transmit oxygen into the bloodstream. In any part of the body, scarring occurs when cells called fibroblasts, an important part of normal wound healing, make collagen to reinforce the healing matrix that forms over damaged tissue. Normally scarring is limited, but if too many fibroblasts travel to the site of an injury, large amounts of collagen can be deposited, producing excessive, fibrotic scarring. Fibroblasts are known to be present in affected lung tissue in IPF, and previous studies showed that the activity of factors that attract fibroblasts to the site of an injury rises with the severity of the disease. The current study was designed to determine which specific “chemoattractants” were associated with IPF, something not previously known.