Researchers at The University of Alabama at Birmingham have identified idiopathic pulmonary fibrosis as a repurposing opportunity for fasudil, a Rho kinase inhibitor that Asahi Kasei Pharma Corp. markets as Eril to treat aneurysm. The key observation was that the drug acts on a pathway that converts biochemical or biomechanical stimuli into fibrogenic signals that sustain myofibroblast activation and survival.1
The team now needs to develop a formulation of fasudil or other Rho kinase inhibitors that works only in the lung and thus avoids systemic side effects.
In normal wound healing, fibroblasts that reside in tissues are activated and transform into myofibroblasts, which are characterized by high contractile activity that results from actin a2 smooth aorta muscle (ACTA2; a-SMA) accumulation in stress fibers. The myofibroblasts help remodel and repair tissue by secreting extracellular matrix components, such as collagen and fibronectin.
Once the wound is re-epithelialized, the myofibroblasts undergo apoptosis.2
In fibrotic disease, apoptotic-resistant myofibroblasts persist in injured tissues and