Speaker
Description
Idiopathic Pulmonary fibrosis (IPF) characterized by progressive scarring and stiffening of the lungs resulting in irreversible functional impairment followed by death if left untreated for 3-5 years. The impediments in understanding the underlying pathology of the fibrotic events and lack of knowledge about drug targets made the pathophysiology foggy, thus the drugs are being used double blindly in light of only the symptomatic view. Two drugs which are recently approved for lengthening life span namely Nintedenib and Pirfenidone. Nintedenib used in malignancy for anti-angiogenic activity is repurposed for IPF treatment as it also possesses capacity to downregulate various growth factors which contribute to the progression of fibrosis. It acts as a competitive inhibitor of FGFR-1, VEGFR-2 as well as PDGFR-alpha and beta. Pirfenidone, an immunosuppressant, is capable of downregulating molecules like TGF-beta, TNF-alpha and IL-6, playing vital role to combat with the life-threatening disorder. Despite of being the go-to drugs, physicians hesitate to prescribe these drugs due to the adverse side effects like nausea, diarrhoea (mostly), anorexia, immune suppression, weight loss. According to INPULSIS and INSTAGE clinical trial data, discontinuation of the therapy was 14.1% and 16.9%. Patients with severe impaired lung function were excluded in the clinical trial which portrays limitations of these drugs. On the other hand, lungs transplantation is also not feasible due to graft rejection cases. Therefore, it has been a challenge for the researchers to find out the targets to deal this deadly disorder and shift the research trend towards promising therapeutics.