title: Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.
abstract: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.
  
  
  
  This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
authors.affiliation: Center for Science, Health and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Berger
authors.affiliation: EA4475 - Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Besson
authors.affiliation: The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: A Hamid
authors.initials: AH
authors.lastname: Boulares
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, Constance, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, Headache Center - University Hospital, University of Florence, Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
authors.affiliation: Department of Critical Care Medicine and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Clark
authors.affiliation: Newcastle University, Northern Institute for Cancer Research, Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Curtin
authors.affiliation: Department of Pharmacology, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering and Department of Neurology and Department of Pharmacology and Molecular Sciences and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering and Department of Neurology and Department of Physiology and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.affiliation: Department of Surgery and Center for Immunity and Inflammation, Rutgers-New Jersey Medical School, Newark, NJ, USA.
authors.forename: György
authors.initials: G
authors.lastname: Haskó
authors.affiliation: Department of Intensive Care Medicine and Burn Center, University Hospital Medical Center, Faculty of Biology and Medicine, Lausanne, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
authors.affiliation: Department of Neuroscience, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Moroni
authors.affiliation: Laboratory of Physiologic Studies, Section on Oxidative Stress Tissue Injury, NIAAA, NIH, Bethesda, USA.
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.affiliation: Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.affiliation: Radikal Therapeutics Inc., West Tisbury, MA, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Salzman
authors.affiliation: Department of Neurology and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
authors.affiliation: Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Strosznajder
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Sümegi
authors.affiliation: Department of Neurology, University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Swanson
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Csaba
authors.identifier: 0000-0003-3110-4235
authors.initials: C
authors.lastname: Szabo
mesh_terms: D000208:Acute Disease / Q000628:therapy; D000818:Animals; D002908:Chronic Disease / Q000188:drug therapy; D058492:Drug Repositioning / Q000379:methods*; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors