Drug repurposing in idiopathic pulmonary fibrosis filtered by a bioinformatics-derived composite score

IPF is a rare, incurable disease of the respiratory system during which fibrotic tissue and scars appear in the lungs.
It leads to death within 2–5 years after the diagnosis. Early diagnosis is poor due to the nonspecific symptoms of
the disease. Clinical symptoms consist of dyspnea on exertion, dry cough and velcro-like auscultatory. A high resolution
computed tomography (HRCT) of the patient’s lungs is needed to differentiate IPF from other idiopathic
interstitial pneumonias. Finally, a biopsy of the fibrotic areas from the inflammatory parts of the lung epithelium
is needed to accurately determine the existence of IPF. There are different stages of IPF usually labeled as mild or
severe. In our study, we refer to mild cases as early, stable or slow and to severe cases as advanced, acute or rapid in
accordance to each dataset’s samples. New methods of IPF staging have been recently developed based on gender,
age and lung physiology where, given the required measurements, the probability of mortality for the patient
in the next 3 years is calculated1. Molecular mechanisms of IPF have been studied before, including cellular
interactions via a complex cytokine-signalling mechanism, heightened collagen gene expression, signaling events
that mediate fibroblast proliferation and myofibroblasts, cell matrix interactions2, endoplasmic reticulum stress,
shortened telomeres, inflammation and immune mechanisms, oxidative stress and signaling and procoagulant
mechanisms3. There are currently two FDA approved drugs with inhibiting role against IPF; nintedanib and pirfenidone.
Despite that, an actual treatment that completely cures the patient from the disease remains to be found.
Other studies suggest that inhaled interferon gamma aerosol may pose as an effective treatment against
IPF. An 80-week treatment of inhaled interferon-gamma for 10 patients showed significant decrease in profibrotic
cytokines and reversed the decrease in lung capacity and diffusing capacity for carbon monoxide4. Recent
research proposes that the guidelines for diagnosis, prognosis and treatment of IPF should be targeting individuals
in a personalized medicine approach while making use of multi-omics (genomics, proteomics, metabolomics,
microbiomics, etc.) training data sources.