title: New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses.
abstract: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, with a median survival as short as 3 years from the time of diagnosis and no pharmacological therapies yet approved by the U.S. Food and Drug Administration. To address the great unmet need for effective IPF therapy, a number of new drugs have recently been, or are now being, evaluated in clinical trials. The rationales for most of these therapeutic candidates are based on the current paradigm of IPF pathogenesis, in which recurrent injury to the alveolar epithelium is believed to drive aberrant wound healing responses, resulting in fibrosis rather than repair. Here we discuss drugs in recently completed or currently ongoing phase II and III IPF clinical trials in the context of their putative mechanisms of action and the aberrant repair processes they are believed to target: innate immune activation and polarization, fibroblast accumulation and myofibroblast differentiation, or extracellular matrix deposition and stiffening. Placed in this context, the positive results of recently completed trials of pirfenidone and nintedanib, and results that will come from ongoing trials of other agents, should provide valuable insights into the still-enigmatic pathogenesis of this disease, in addition to providing benefits to patients with IPF.
authors.affiliation: Pulmonary and Critical Care Unit and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Neil
authors.initials: N
authors.lastname: Ahluwalia
authors.forename: Barry S
authors.initials: BS
authors.lastname: Shea
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D011728:Pyridones; C093844:pirfenidone; C530716:nintedanib
keywords: idiopathic pulmonary fibrosis; investigational treatments; pathogenesis
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