REPURPOSING ZOLEDRONATE FOR IDIOPATHIC PULMONARY FIBROSIS – A NOVEL THERAPEUTIC APPROACH

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring with a median survival time of 3-4-years postdiagnosis.

It is associated with increasing cough, dyspnea, and impaired quality of life, affecting more than 2 000 individuals in Sweden. IPF is thought to be driven by chronic epithelial injury-repair responses resulting in fibrosis.

Current IPF therapies (nintedanib and pirfenidone) focus on the inhibition of collagen deposition with limited success in achieving overall IPF resolution, necessitating the need for novel therapies.

In a murine model of IPF we repurposed zoledronic acid (ZA), a drug used to treat osteoporosis, finding that it strongly reduced pulmonary fibrosis.In this project, we aim to perform a randomized, placebo-controlled trial, repurposing ZA to treat IPF, in addition to ongoing antifibrotic treatment. ZA will be administered at monthly intervals for 24 or 52 weeks with endpoint measures after 12, 24, and 52 weeks.

The primary endpoint will be change in forced vital capacity (FVC) and secondary endpoints health-related quality of life, walk  test to measure physical endurance, and gas diffusion capacity.

Part of the pre-study will also be epidemiological studies, where effects from ZA and other bisphosphonates on the risk of IPF will be investigated.

Drug repurposing allows for shortened development of novel treatments, allowing patients to benefit from less expensive medications.