Pulmonary fibrosis is a lung condition involving excessive scarring that affects patients’ breathing, and currently can’t be cured. But now, scientists at the University of Alabama have found a way to reverse the condition in mice, using a drug that’s already available for other uses.
In patients with idiopathic pulmonary fibrosis (IPF), lung tissue becomes scarred due to an abnormal healing process that deposits too much collagen. That reduces lung tissue’s ability to absorb oxygen from the air, leading to shortness of breath, coughing, fatigue, and chest pain. Treatment can slow progression of the disease, but there’s no cure, and it has a high mortality rate within a few years.
But in the new study, researchers have found a way to completely reverse the condition in mice. The key is a drug called ABT-199, which conveniently enough has already been approved by the FDA for use in treating some types of leukemia. The team treated mice that had lung fibrosis with a daily dose of ABT-199, and after 21 days their lung architecture had returned to normal, with no collagen deposition.
The researchers made the discovery after noticing that human patients with IPF had higher amounts of a protein called Bcl-2 in their lung immune cells. Bcl-2 regulates apoptosis, the process of programmed cell death, and elevated levels of this protein meant that the immune cells, known as macrophages, refused to die off when their work was done. This seemed to lead to the damage of IPF.
To test the correlation, the team then engineered mice to lack the Bcl-2 gene. Sure enough, these mice seemed to be protected from pulmonary fibrosis, induced by asbestos and certain drugs that normally cause the condition. This eventually led the researchers to test ABT-199, which works by inhibiting Bcl-2.
While the work is still in the very early stages, the team says that it could unlock a new target for future therapies for pulmonary fibrosis in humans.
The research was published in the Nature journal Cell Death & Differentiation.
Source: University of Alabama
