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

Lookup NU author(s): Professor Nicola CurtinORCiD

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Abstract

© 2017 The British Pharmacological Society. 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.

Publication metadata

Author(s): Berger NA, Besson VC, Boulares AH, Burkle A, Chiarugi A, Clark RS, Curtin NJ, Cuzzocrea S, Dawson TM, Dawson VL, Hasko G, Liaudet L, Moroni F, Pacher P, Radermacher P, Salzman AL, Snyder SH, Soriano FG, Strosznajder RP, Sumegi B, Swanson RA, Szabo C

Publication type: Article

Publication status: Published

Journal: British Journal of Pharmacology

Year: 2018

Volume: 175

Issue: 2

Pages: 192-222

Print publication date: 01/01/2018

Online publication date: 18/02/2017

Acceptance date: 13/02/2017

ISSN (print): 0007-1188

ISSN (electronic): 1476-5381

Publisher: John Wiley & Sons Ltd

URL: https://doi.org/10.1111/bph.13748

DOI: 10.1111/bph.13748

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