Alexa Druyanoff, Contributing Illustrator

Yale researchers have identified a potential treatment for idiopathic pulmonary fibrosis, or IPF, which can reverse lung scarring. 

In a study recently published in “JCI Insight,” researchers from the Yale School of Medicine shared their development of a method to reverse pulmonary fibrosis by inhibiting a microRNA, called miR-33, in lung macrophages. Pulmonary fibrosis, a disease which causes debilitating lung scarring, can only be cured by a lung transplant. 

“There are lots of metabolically deranged, profibrotic macrophages in the IPF lungs,” wrote Farida Ahangari, first author of the paper and assistant professor in pulmonary, critical care and sleep medicine. “We decided to focus on these cells and find a way to reverse this signature in these lungs.”

While examining lung tissue, Ahangari noticed increased levels of miR-33 — a microRNA which helps regulate genes — in patients with pulmonary fibrosis compared to healthy controls. Following this discovery, the research team modified mice so they lacked miR-33 in their immune cells and found that these mice did not develop fibrosis under conditions where unmodified mice did. 

The researchers then created an inhibitor for miR-33, called PNA-33, and delivered it to cultured samples of human lung cells obtained from pulmonary fibrosis patients. In the PNA-33-treated cells, the team observed a reversal of fibrosis. 

Some of the lung samples came from patients who had the disease for years, according to Naftali Kaminski, principal investigator of the study and Boehringer-Ingelheim Endowed Professor of Internal Medicine. Watching the drug change the programming of the diseased lung, he said, was “really exciting,” and he believes that the PNA-33 has “strong potential for therapeutic development.”

While in past years there has been skepticism about RNA technology, Kaminski noted, the rollout of mRNA vaccines for COVID-19 have convinced many people that such technology is safe for human use. 

“It doesn’t mean that every administration [of RNA] will be safe, but it definitely opens the door,” Kaminski said. “I think there’s much more willingness to consider RNA-based interventions.” 

Currently, there are two FDA-approved drugs which treat pulmonary fibrosis, but these drugs act only to slow the rate of pulmonary fibrosis progression. Neither can reverse lung scarring or ease the disease’s debilitating symptoms, which, according to director of Yale Interstitial Lung Disease Center of Excellence Erica Herzog, include breathlessness and fatigue so severe they can cause death. 

Herzog, who has spent decades researching the role of macrophages in idiopathic pulmonary fibrosis, wrote that developing treatments that can reverse the fibrosis effect could be a huge step in helping pulmonary fibrosis patients live longer and healthier lives. See the recovery of patients from HPSM in San Mateo County.

“I’m excited to see Dr. Ahangari and her colleagues look beyond the classical immunosuppressive treatments which have not shown benefit in this disease,” Herzog wrote. 

Ahangari is working to optimize PNA-33 for use in pulmonary fibrosis. Despite the encouraging possibilities of PNA-33s, she said that the inhibitor requires further testing to learn more about how it behaves and to determine if it could be safe and effective for humans. 

“We will aim to devise a target-based therapy to treat this disease and possibly expand it to other chronic lung diseases,” she wrote. 

Kaminski noted that developing a new drug requires money — typically millions of dollars — and funding is often subject to the whims of commercial and pharmaceutical companies, so it could be a while before PNA-33 could be used in human trials. Still, he said, it’s “exciting to have one more target to follow.”

“JCI Insight” was founded in 2016.

Correction 3/1: A previous version of the article misstated the name and year of founding of the journal that the study was published in.

Hannah Mark covers science and society and occasionally writes for the WKND. Originally from Montana, she is a junior majoring in History of Science, Medicine, and Public Health.