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Br J Pharmacol. 2018 Jan;175(2):192-222. doi: 10.1111/bph.13748. Epub 2017 Mar 26.

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.

Author information

1
Center for Science, Health and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
2
EA4475 - Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
3
The Stanley Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
4
Molecular Toxicology Group, Department of Biology, University of Konstanz, Constance, Germany.
5
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, Headache Center - University Hospital, University of Florence, Florence, Italy.
6
Department of Critical Care Medicine and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
7
Newcastle University, Northern Institute for Cancer Research, Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK.
8
Department of Pharmacology, University of Messina, Messina, Italy.
9
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.
10
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.
11
Department of Surgery and Center for Immunity and Inflammation, Rutgers-New Jersey Medical School, Newark, NJ, USA.
12
Department of Intensive Care Medicine and Burn Center, University Hospital Medical Center, Faculty of Biology and Medicine, Lausanne, Switzerland.
13
Department of Neuroscience, Università degli Studi di Firenze, Florence, Italy.
14
Laboratory of Physiologic Studies, Section on Oxidative Stress Tissue Injury, NIAAA, NIH, Bethesda, USA.
15
Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital, Ulm, Germany.
16
Radikal Therapeutics Inc., West Tisbury, MA, USA.
17
Department of Neurology and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
18
Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
19
Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
20
Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
21
Department of Neurology, University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
22
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.

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.

LINKED ARTICLES:

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.

PMID:
28213892
PMCID:
PMC5758399
DOI:
10.1111/bph.13748
[Indexed for MEDLINE]
Free PMC Article

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