Journal article
Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP-Ribose) Polymerase Inhibitor Veliparib
Journal of the American Heart Association, Vol.14(19), e040914
10/07/2025
DOI: 10.1161/JAHA.124.040914
PMCID: PMC12684482
PMID: 40996065
Abstract
The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1 month. The PARP (poly(ADP-ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (
=231 veliparib;
=344 placebo).
A secondary analysis was performed to evaluate veliparib treatment on primary and secondary outcomes in individual subgroup models.
Intravenous injection of veliparib at reperfusion failed to show a benefit on the corner test at 7 or 30 days of recovery in young mice, obese mice, or spontaneously hypertensive rats. However, in aging mice (15-18 months old), veliparib significantly improved performance on the corner test at 7 (
=0.007) and 30 (
=0.03) days and reduced foot-faults on the grid walk test at 7 (
=0.024) and 30 (
=0.008) days. These effects were independent of sex. Treatment had no effect on magnetic resonance imaging-determined lesion volume. The survival was similar with placebo and veliparib treatments across subgroups, although mortality was high in aging mice.
Veliparib improved functional outcome in aging mice. Because ischemic stroke predominantly occurs in the aging population, further research into the benefit of PARP inhibitors in aged animal models of stroke is warranted.
Details
- Title: Subtitle
- Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP-Ribose) Polymerase Inhibitor Veliparib
- Creators
- Raymond C Koehler - Johns Hopkins UniversityKarni Bedirian - Icahn School of Medicine at Mount SinaiMu-Hsun Chen - Icahn School of Medicine at Mount SinaiYanrong Shi - Johns Hopkins UniversitySuyi Cao - Johns Hopkins UniversityBrooklyn D Avery - Johns Hopkins UniversitySenthilkumar S Karuppagounder - Johns Hopkins UniversityKazi Akhter - Johns Hopkins UniversityAdnan Bibic - Johns Hopkins UniversityValina L Dawson - Johns Hopkins UniversityTed M Dawson - Johns Hopkins UniversityMárcio A Diniz - Icahn School of Medicine at Mount SinaiJessica Lamb - University of Southern CaliforniaKarisma A Nagarkatti - University of Southern CaliforniaAnjali Chauhan - The University of Texas Health Science Center at HoustonJaroslaw Aronowski - The University of Texas Health Science Center at HoustonLouise D McCullough - The University of Texas Health Science Center at HoustonAndreia Lopes de Morais - Harvard Medical SchoolXuyan Jin - Massachusetts General HospitalCenk Ayata - Massachusetts General HospitalMariia Kumskova - University of IowaRakesh B Patel - University of IowaAnil K Chauhan - University of IowaEnrique C Leira - University of IowaPradip K Kamat - Augusta UniversityMohammad B Khan - Augusta UniversityKrishnan M Dhandapani - Augusta UniversityDavid C Hess - Augusta UniversityLigia S B Boisserand - Yale UniversityBasavaraju G Sanganahalli - Yale UniversityLauren H Sansing - Yale UniversityPatrick D Lyden - University of Southern CaliforniaSPAN investigators
- Resource Type
- Journal article
- Publication Details
- Journal of the American Heart Association, Vol.14(19), e040914
- DOI
- 10.1161/JAHA.124.040914
- PMID
- 40996065
- PMCID
- PMC12684482
- NLM abbreviation
- J Am Heart Assoc
- ISSN
- 2047-9980
- eISSN
- 2047-9980
- Publisher
- WILEY
- Grant note
- National Institutes of Health: U01NS113444, UO1NS113356, U01 NS113443, U01NS113388, U01NS113445, U01NS113451, U24NS113452
SPAN 1 was supported by grants from the National Institutes of Health: U01NS113444 (RCK, Johns Hopkins University), UO1NS113356 (DH, Augusta University), U01 NS113443 (CA, Massachusetts General Hospital), U01NS113388 (AKC and EL, University of Iowa), U01NS113445 (LHS, Yale University), U01NS113451 (LDM and JA, University of Texas), U24NS113452 (PDL, University of Southern California).
- Language
- English
- Electronic publication date
- 09/25/2025
- Date published
- 10/07/2025
- Academic Unit
- Neurology; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984966544102771
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