Journal article
Uric Acid: A Translational Journey in Cerebroprotection That Spanned Preclinical and Human Data
Neurology, Vol.101(23), pp.1068-1074
12/05/2023
DOI: 10.1212/WNL.0000000000207825
PMCID: PMC10752646
PMID: 37848338
Abstract
Uric acid (UA) is a strong endogenous antioxidant that neutralizes the toxicity of peroxynitrite and other reactive species on the neurovascular unit generated during and after acute brain ischemia. The realization that a rapid reduction of UA levels during an acute ischemic stroke was associated with a worse stroke outcome paved the way to investigate the value of exogenous UA supplementation to counteract the progression of redox-mediated ischemic brain damage. The long translational journey for UA supplementation recently reached a critical milestone when the results of the multicenter NIH stroke preclinical assessment network (SPAN) were reported. In a novel pre-clinical paradigm, six treatment candidates including UA supplementation were selected and tested in six independent laboratories following predefined criteria and strict methodological rigor. UA supplementation was the only intervention in SPAN that exceeded the pre-specified efficacy boundary with males and females, young mice, young rats, aging mice, obese mice, and spontaneously hypertensive rats. This unprecedented achievement will allow UA to undergo clinical testing in a pivotal clinical trial through a NIH Strokenet Thrombectomy Endovascular Platform (STEP) created to assess new treatment strategies in patients treated with mechanical thrombectomy. UA is a particularly appealing adjuvant intervention for mechanical thrombectomy, as it targets the microcirculatory hypoperfusion and oxidative stress that limits the efficacy of this therapy. This descriptive review aims to summarize the translational development of UA supplementation, highlighting those aspects that likely contributed to its success. It includes having a well-defined target and mechanism of action, and an approach that simultaneously integrated rigorous pre-clinical assessment, with epidemiological and preliminary human intervention studies. Validation of the clinical value of UA supplementation in a pivotal trial would confirm the translational value of the SPAN paradigm in pre-clinical research.
Details
- Title: Subtitle
- Uric Acid: A Translational Journey in Cerebroprotection That Spanned Preclinical and Human Data
- Creators
- Enrique Leira - University of IowaAnna M Planas - Institut d'Investigacions Biomèdiques de BarcelonaAnil K Chauhan - University of IowaAngel Chamorro - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.101(23), pp.1068-1074
- DOI
- 10.1212/WNL.0000000000207825
- PMID
- 37848338
- PMCID
- PMC10752646
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Language
- English
- Electronic publication date
- 10/17/2023
- Date published
- 12/05/2023
- Academic Unit
- Neurology; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984479554902771
Metrics
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