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 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

Research output: Contribution to journalArticle

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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Acute Lung Injury
Therapeutics
Septic Shock
DNA Repair
Pancreatitis
Multiple Sclerosis
Parkinson Disease
Chronic Disease
Asthma
Stroke
Odds Ratio
Poly(ADP-ribose) Polymerase Inhibitors
Enzymes
olaparib
Traumatic Brain Injury

ASJC Scopus subject areas

  • Pharmacology

Cite this

Berger, N. A., Besson, V. C., Boulares, A. H., Bürkle, A., Chiarugi, A., Clark, R. S., ... 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

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. / Berger, Nathan A.; Besson, Valerie C.; Boulares, A. Hamid; Bürkle, Alexander; Chiarugi, Alberto; Clark, Robert S.; Curtin, Nicola J.; Cuzzocrea, Salvatore; Dawson, Ted M; Dawson, Valina; Haskó, György; Liaudet, Lucas; Moroni, Flavio; Pacher, Pál; Radermacher, Peter; Salzman, Andrew L.; Snyder, Solomon H; Soriano, Francisco Garcia; Strosznajder, Robert P.; Sümegi, Balázs; Swanson, Raymond A.; Szabo, Csaba.

In: British Journal of Pharmacology, 2017.

Research output: Contribution to journalArticle

Berger, NA, Besson, VC, Boulares, AH, Bürkle, A, Chiarugi, A, Clark, RS, Curtin, NJ, Cuzzocrea, S, Dawson, TM, Dawson, V, Haskó, G, Liaudet, L, Moroni, F, Pacher, P, Radermacher, P, Salzman, AL, Snyder, SH, Soriano, FG, Strosznajder, RP, Sümegi, B, Swanson, RA & Szabo, C 2017, '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
Berger, Nathan A. ; Besson, Valerie C. ; Boulares, A. Hamid ; Bürkle, Alexander ; Chiarugi, Alberto ; Clark, Robert S. ; Curtin, Nicola J. ; Cuzzocrea, Salvatore ; Dawson, Ted M ; Dawson, Valina ; Haskó, György ; Liaudet, Lucas ; Moroni, Flavio ; Pacher, Pál ; Radermacher, Peter ; Salzman, Andrew L. ; Snyder, Solomon H ; Soriano, Francisco Garcia ; Strosznajder, Robert P. ; Sümegi, Balázs ; Swanson, Raymond A. ; Szabo, Csaba. / Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. In: British Journal of Pharmacology. 2017.
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