Evidence map›Paper›PMID 28622913›Full record

ReviewExperimental neurology2017

Targeting urate to reduce oxidative stress in Parkinson disease.

Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Experimental neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
8.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Plasma urate concentrations and possible REM sleep behavior disorder.Annals of clinical and translational neurology · 2019
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Grace F CrottyDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: gcrotty@partners.org.
Alberto AscherioDepartments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA, USA.
Michael A SchwarzschildDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Massachusetts General Hospital · USHarvard University · US

Funding

Phase 3 trial of inosine for Parkinson's disease CCCU01NS090259 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2015 to 2019
$16.9M
Translational Foundation of Adenosine Antagonist Use for DyskinesiasR01NS054978 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2006 to 2010
$2.1M
Pursuing purinergic pathways to clinical trials for Parkinson's diseaseK24NS060991 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2008 to 2012
$954k
Targeting Adenosine A2A Receptors in Parkinson's DiseaseR13NS055597 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2006 to 2006
$10k
NINDS NIH HHS K24 NS060991NINDS NIH HHS R01 NS054978NINDS NIH HHS R13 NS055597NINDS NIH HHS U01 NS090259
6 · The paper itself

Abstract

Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants. Urate, the main antioxidant found in plasma as well as the end product of purine metabolism in humans, has emerged as a promising potential neuroprotectant with advantages that distinguish it from previously tested antioxidant agents. Uniquely, higher urate levels in plasma or cerebrospinal fluid (CSF) have been linked to both a lower risk of developing PD and to a slower rate of its subsequent progression in numerous large prospective epidemiological and clinical cohorts. Laboratory evidence that urate confers neuroprotection in cellular and animal models of PD, possibly via the Nrf2 antioxidant response pathway, further strengthened its candidacy for rapid clinical translation. An early phase trial of the urate precursor inosine demonstrated its capacity to safely produce well tolerated, long-term elevation of plasma and CSF urate in early PD, supporting a phase 3 trial now underway to determine whether oral inosine dosed to elevate urate to concentrations predictive of favorable prognosis in PD slows clinical decline in people with recently diagnosed, dopamine transporter-deficient PD.

Indexed as

AnimalsAntioxidantsDisease ProgressionHumansNeuroprotective AgentsOxidative StressParkinson DiseaseUric AcidAntioxidantsNeuroprotective AgentsUric AcidAntioxidantBiomarkerEpidemiologyMitochondrial dysfunctionNrf2 activator neuroprotectionOxidative stressParkinson diseaseUrateUric acid

Identifiers

PMID28622913
PMCPMC5693633
OpenAlexW2626775758

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.