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

Nathan A. Berger, Valerie C. Besson, A. Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S. Clark, Nicola J. Curtin, Salvatore Cuzzocrea, Ted M. Dawson, Valina L. Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L. Salzman, Solomon H. Snyder, Francisco Garcia Soriano, Robert P. Strosznajder, Balázs SümegiRaymond A. Swanson, Csaba Szabo

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    47 Scopus citations

    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.

    Original languageEnglish (US)
    JournalBritish Journal of Pharmacology
    DOIs
    StateAccepted/In press - 2017

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    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Berger, N. A., Besson, V. C., Boulares, A. H., Bürkle, A., Chiarugi, A., Clark, R. S., Curtin, N. J., Cuzzocrea, S., Dawson, T. M., Dawson, V. L., Haskó, G., Liaudet, L., Moroni, F., Pacher, P., Radermacher, P., Salzman, A. L., Snyder, S. H., Soriano, F. G., Strosznajder, R. P., ... Szabo, C. (Accepted/In press). Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. British Journal of Pharmacology. https://doi.org/10.1111/bph.13748