Researchers who studied the drug eperisone, which preferentially suppresses fibroblast activity, found that it has therapeutic potential in treating idiopathic pulmonary fibrosis (IPF), according to results of a new study published in Cell Death Discovery

IPF is characterized in later stages by the appearance of severe fibrosis, which manifests in clinical imaging as a honeycomb lung. Steroids and immunosuppressants are used to treat IPF, but these medications are largely unable to stop IPF disease progression.

Newer medications, such as pirfenidone and nintedanib, have antifibrotic properties and have been shown to improve forced vital capacity, but concerns surrounding the severity of the adverse effects reported remain. Although the exact etiology of IPF is unknown, there are theories on various aspects of the disease, including how lung remodeling occurs.


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“Thus, it is important to identify compounds that inhibit transdifferentiation of fibroblasts into myofibroblasts or inhibit activation of myofibroblasts,” the authors wrote. This theory highlights the role of the myofibroblast in promoting the process of pathological lung fibrosis.

Read more about IPF etiology 

On the basis of this theory, the drug eperisone, which is a muscle relaxant that also acts preferentially on lung fibroblasts, should demonstrate some therapeutic effect in disrupting the lung fibrosis process. The researchers purchased Institute of Cancer Research mice from Japan to complete the study. IPF-like conditions in the mice were induced through the administration of bleomycin (BLM).

The mice were then administered the drugs eperisone, tolperisone, pirfenidone, or nintedanib for a total of 9 days. Another study investigated the adverse effects of eperisone by administering 250 mg/kg orally once. The dose administered was 5 times the amount that showed efficacy. Twenty-four hours later, various samples were extracted and analyzed. 

The results confirmed that eperisone inhibited pulmonary fibrosis, respiratory dysfunction, and fibroblast activation in the IPF mouse models. While pirfenidone and nintedanib did inhibit BLM-induced pulmonary fibrosis, they did so less effectively compared to eperisone. In addition, eperisone demonstrated an acceptable safety profile, neither inducing adverse effects in the liver or the gastrointestinal tract in the mouse models studied. 

“Considering these results, we propose that eperisone may be safer and more therapeutically beneficial for IPF patients than current therapies,” Tanaka and colleagues concluded. This was likely the first time that eperisone was tested in a BLM-induced pulmonary fibrosis model.

Reference

Tanaka K, Shimoda M, Sugizaki T, et al. Therapeutic effects of eperisone on pulmonary fibrosis via preferential suppression of fibroblast activityCell Death Discov. 2022;8(1):52. doi:10.1038/s41420-022-00851-7