Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 175, Issue 2, Pages 192-222Publisher
WILEY
DOI: 10.1111/bph.13748
Keywords
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Categories
Funding
- [P50 NS38377]
- [P50 DA00266]
- [R37 NS67525]
- [P50 GM060338]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P30GM114732, P30GM106392, P50GM060338] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R37NS067525, R01NS081149, P50NS038377] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [ZIAAA000375] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P50DA000266] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX003249] Funding Source: NIH RePORTER
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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.
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