Can this diabetes drug treat lung disorder?

A drug used to treat diabetes can reverse a fatal lung disorder, scientists have found for the first time. Despite significant advances to reveal the pathological mechanisms of persistent fibrosis, effective treatment interventions are lacking.

Pulmonary fibrosis can develop after lung injuries like infections, radiation or chemotherapy, or it can have an unknown cause, as in idiopathic pulmonary fibrosis, or IPF. IPF is a progressive, and ultimately fatal, lung disorder that strikes more than five million worldwide.

In experiments using lung tissues from patients with IPF, mouselung fibroblasts and a murine model of lung fibrosis, researchers from University of Alabama at Birmingham in the US showed the reversal of lung fibrosis and the underlying cellular mechanisms affected by the drug treatment.

Activation of AMPK in myofibroblasts from lungs of humans with IPF, using the drug metformin or another activator called AICAR, led to lower fibrotic activity. AMPK activation also enhanced the production of new mitochondria, the organelles in cells that produce energy, in the myofibroblasts, and it normalised the cells’ sensitivity to apoptosis.

The drug that accelerated the resolution of lung fibrosis is metformin, which is a safe and widely used agent for non-insulin-dependent diabetes. The research focused on AMP-activated protein kinase (AMPK), an enzyme that senses energy state in the cell and regulates metabolism.

It found that AMPK activity was lower in myofibroblast cells within fibrotic regions of human lung tissue from IPF patients. Myofibroblasts deposit extracellular collagen fibre as part of the fibrosis process. These myofibroblasts were metabolically active and were resistant to the programmed cell death called apoptosis, a natural process that removes more than 50 billion damaged or aged cells in adults each day.