Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Repurposing Pyrvinium as an Inhalation Therapy for Idiopathic Pulmonary Fibrosis

Award Number: R41HL180136
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Repurposing Pyrvinium as an Inhalation Therapy for Idiopathic Pulmonary Fibrosis - SUMMARY Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease that is characterized by progressive decline in lung function due to inflammatory and fibrotic changes of the lung parenchyma. The average life expectancy for patients is only 3-5 years, resulting in the deaths of 40,000 patients each year in the US. There are only two FDA-approved drugs for IPF that slow disease progression but do not prevent or reverse symptoms or pathology, and they exhibit significant side effects in many patients. Promising drugs are in development, but recent clinical trial failures emphasize the need for additional therapeutic approaches. IPF begins following an insult to the tissue microenvironment, resulting in a loss of alveolar cells, growth of activated fibroblasts (myofibroblasts), and increased deposition of extracellular matrix proteins, like collagen, leading to scarring, increased tissue stiffness, and the inability to breathe followed by death. Many cell signaling pathways contribute to this pathology, including TGFβ signaling. A high content imaging screen was used to discover that the FDA- approved pinworm drug pyrvinium (pyr) blocks TGFβ-induced fibrosis. Subsequent studies showed pyr activated casein kinase 1α and downregulated the YAP/TAZ signaling pathway. Pyr appeared efficacious in a variety of in vitro assays and in vivo studies (intraperitoneal route), but bioavailability problems presented a challenge for oral administration. Inhalation dosing allows for direct drug delivery to the site of action and may reduce the possibility of off-target organ toxicity. In preliminary acute toxicity studies, pyr was well-tolerated when administered as a nebulized aqueous solution to mice, but efficacy was not tested. Therefore, the following aims are proposed to further develop pyr as an experimental IPF therapeutic designed for inhaled administration. In Aim 1, pyr will be administered by oropharyngeal aspiration beginning after administration of bleomycin, a treatment resulting in progressive fibrosis over 3 months. A second animal model will involve administration to lungs of an adenovirus expressing TGFβ to induce fibrosis. Lungs will be analyzed by histopathological and biochemical approaches to measure extracellular matrix remodeling, fibrosis, cell proliferation and measures of toxicity. This study will determine if pyr is safe and effective in two relevant mouse models when administered via inhalation. Aim 2 will test the ability of pyr to repress fibrosis in ex vivo human precision-cut lung slice tissue from healthy and IPF patient donors. Assays will include a hydroxyproline assay for collagen, immunoblotting, and qRT-PCR analysis to measure activity of fibrosis-associated signaling pathways, automated imaging to quantify alveolar and fibroblast cell density, and histological staining to score changes in cell morphology and tissue architecture. This study will reveal if pyr can inhibit and reverse fibrosis in a human ex vivo model, adding relevance to outcomes of the mouse studies, and will be used to test the proposed mechanisms of action for pyr. These data will also inform the design of IND-enabling safety and pharmacology studies in preparation for a Phase 1 clinical trial.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	OLEOLIVE, INC.	2031 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Lung Diseases Research	000	1	2/11/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $309,418 )
2025	2025	OLEOLIVE, INC.	2031 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Lung Diseases Research	000	1	9/17/2025	NEW	$309,418
														Subtotal = $309,418

Grand Total All Awards = $309,418

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Repurposing Pyrvinium as an Inhalation Therapy for Idiopathic Pulmonary Fibrosis

Award Number: R41HL180136

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer