Diagnosis of IPF is typically made by process of elimination of similar disease states such as interstitial lung diseases (ILD’s). IPF is often distinguished from other diseases by its poor prognosis and unresponsiveness to therapy.
It is thought that IPF is caused by a combination of loss of healthy lung cells, plus new growth of unwanted fibrotic cells. This dysregulation likely involves an imbalance of two biological pathways, with healthy cells being turned off while unwanted cells are turned on.
Palliative treatments for IPF can alleviate symptoms which include chest pain, cough and shortness of breath. However, current drugs appear only to slow the proliferation of unwanted fibrotic cells without protecting the survivability of alveolar epithelial cells (AEC’s).
New research has shown that disrupting the biological cross-talk in the fibrinolytic system may be a novel point of drug intervention for IPF. Targeting the AEC survival pathway appears to be unique among IPF drugs, potentially resolving fibrosis and restoring healthy lung function.
Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by progressive tissue scarring that prevents proper lung function. “Idiopathic” means the cause of the disease is unknown, although its origin is possibly genetic or as a result of injury. IPF typically presents in adults 65 or older, and is usually fatal 3-5 years after diagnosis. IPF kills at least 5 in 100,000 patients each year due to respiratory failure.1
Until recently, there were no drug therapies for IPF, with treatments including lung rehabilitation, oxygen therapy, and in advanced cases, lung transplantation. In 2014, anti-fibrotic drugs received approval for treatment of IPF, although these drugs appear only to slow the progression of IPF and do not prevent or reverse the disease. Given the lack of disease resolution, adverse side effects, and financial burden of these currently approved therapies, there is great interest in improving clinical outcomes with new drugs and new treatment pathways.
Although IPF is not fully understood, research has shown that the disease likely involves an altered biological signaling of alveolar epithelial cell (AEC) survival and fibrotic cell removal. Cross-talk in the fibrinolytic system results in dysregulation, giving rise to pulmonary fibrosis. It is generally understood that healthy AEC’s secrete factors that keep fibrocytes and myofibroblasts at bay, and yet no current drugs appear to target AEC survival. With new drug compounds to intervene in the AEC pathway, there is hope not only to slow the disease, but to resolve fibrosis.
Lung Therapeutics is currently developing LTI-03 for the treatment of Idiopathic Pulmonary Fibrosis. The drug is thought to operate through a novel mechanism and addresses a pathway currently not targeted by other therapeutic candidates. Preclinical evidence has shown that LTI-03 triggers both survival signals for alveolar epithelial cells (AEC’s) and destruction signals for unwanted fibrotic cells. Tipping the balance of these biological signals may not only slow the progress of the disease but also restore healthy lung function. This represents the potential for a radical change in both the projected outcome and the financial burden of lung fibrosis treatment, offering new hope for IPF patients.
1 Raghu, Ganesh, Harold R. Collard, Jim J. Egan, Fernando J. Martinez, Juergen Behr, Kevin K. Brown, Thomas V. Colby, et al. 2011. “An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management.” American Journal of Respiratory and Critical Care Medicine 183 (6): 788–824.