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Can Small RNA Inhibitors Reverse Pulmonary Fibrosis?

August 25, 2023
by Melanie Ho

Farida Ahangari, MD, assistant professor (pulmonary), leads a team in the Kaminski lab at Yale School of Medicine (YSM) investigating a new therapeutic approach for pulmonary fibrosis involving the inhibition of a small RNA molecule in the lungs. Their research project is titled, “Targeting Profibrotic Macrophages Using Mir-33 Inhibitors, a Novel Therapeutic Approach for Pulmonary Fibrosis.”

Pulmonary fibrosis is a deadly disease characterized by harmful scarring and stiffening of the lung tissue, which causes difficulty breathing. When the underlying cause of the condition is unknown, the condition is referred to as idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis usually live three to five years after their initial diagnosis. Available treatments for pulmonary fibrosis slow disease progression but do not cure or improve patients’ symptoms and can have substantial side effects.

“As a physician and a scientist, my hope and my passion are to find a safe and efficient drug to ease people’s pain,” said Ahangari.

Pro-fibrotic macrophages are immune cells that contribute to harmful scarring in the lungs. Importantly, these macrophages' metabolic functions are controlled by the microRNA-33 (miR-33). Previously, YSM researchers have found higher levels of miR-33 in cells isolated from patients with idiopathic pulmonary fibrosis compared with healthy patients.

In this project, Ahangari and colleagues are designing and testing drugs that inhibit miR-33 and thereby improve the metabolic functions of lung macrophages.

Ahangari is one of eleven faculty members to receive a 2023 Blavatnik Award from the Blavatnik Fund for Innovation at Yale, which is funding the research. The award “supports innovative Yale investigator-initiated research at all levels. The goal of completed projects are partnerships with industry, through licenses to existing biopharmaceutical companies and startups or industry-sponsored research agreements,” according to Yale Ventures.

“The award acts as a bridge between academia and the industry. Working with the pharmaceutical industry can provide us with the resources to actualize our research, and we can already begin to see the pieces coming together. We are optimistic we will be helping to facilitate the development of our drug to treat lung fibrosis,” said Ahangari.

“At Yale, as in other leading academic institutions, there is no shortage of discoveries that could improve the life of patients with pulmonary fibrosis. The challenge is bringing these discoveries to our patients. I hope that awards such as this one will allow us to overcome this challenge,” said Naftali Kaminski, MD, Boehringer-Ingelheim Pharmaceuticals Professor of Medicine (Pulmonary), chief of Pulmonary, Critical Care & Sleep Medicine, and previous Blavatnik awardee.

In addition to Ahangari and Kaminski, YSM researcher Carlos Fernandez-Hernando, PhD, Anthony N. Brady Professor of Comparative Medicine and of Pathology and director of the Vascular Biology & Therapeutics Program, contributed to the project, along with Raman Bahal, PhD, associate professor of pharmaceutics in the Department of Pharmaceutical Sciences at the University of Connecticut School of Pharmacy. Also, many postdoctoral associates, students, and colleagues at Yale School of Medicine and the University of Connecticut have contributed to their research into using miR-33 inhibitors for pulmonary fibrosis.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within Yale School of Medicine’s Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSM's website, or follow them on Facebook and Twitter.

Submitted by Julie Parry on August 25, 2023