Evidence map›Paper›PMID 39500625›Full record

ArticleCNS neuroscience & therapeutics2024

Targeting Myeloperoxidase to Reduce Neuroinflammation in X-Linked Dystonia Parkinsonism.

Tiziana Petrozziello, Negin Jalali Motlagh, Ranee Zara B Monsanto, Dan Lei, Micaela G Murcar, Ellen B Penney, D Cristopher Bragg, Cara Fernandez-Cerado, G Paul Legarda, Michelle Sy and 8 more

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Myelin pathology is a key feature of X-linked Dystonia Parkinsonism.bioRxiv : the preprint server for biology · 2025
    Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Tiziana PetrozzielloSean M. Healey & AMG Center for ALS at Mass General, Massachusetts General Hospital, Boston, Massachusetts, USA.
Negin Jalali MotlaghDepartment of Radiology, Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ranee Zara B MonsantoSean M. Healey & AMG Center for ALS at Mass General, Massachusetts General Hospital, Boston, Massachusetts, USA.
Dan LeiDepartment of Neurology Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Micaela G MurcarDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ellen B PenneyDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
D Cristopher BraggDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Cara Fernandez-CeradoSunshine Care Foundation, Roxas City, Capiz, Philippines.
G Paul LegardaSunshine Care Foundation, Roxas City, Capiz, Philippines.
Michelle SySunshine Care Foundation, Roxas City, Capiz, Philippines.
Edwin MuñozDepartment of Pathology, College of Medicine, University of the Philippines, Manila, Philippines.
Mark C AngDepartment of Pathology, College of Medicine, University of the Philippines, Manila, Philippines.
Cid Czarina E DiestaDepartment of Neurosciences, Makati Medical Center, Makati, Philippines.
Can ZhangDepartment of Neurology Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Rudolph E TanziDepartment of Neurology Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Irfan A QureshiBiohaven Pharmaceuticals Inc., New Haven, Connecticut, USA.
John W ChenDepartment of Radiology, Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ghazaleh Sadri-VakiliSean M. Healey & AMG Center for ALS at Mass General, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0003-3435-3544

Funding

Assembling the Genetic Architecture of X-linked Dystonia ParkinsonismR01NS102423 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI David Cristopher Bragg, Clotilde Lagier-Tourenne · 2017 to 2026
$5.4M
PET Imaging of Damaging Neuroinflammation in Alzheimer's Disease Technical and Business Assistance (TABA)R44AG079734 · NIA · EINSENCA INC. · PI LARSON, ANDREW CHRISTIAN · 2022 to 2024
$3.0M
Developing a PET tracer targeting myeloperoxidase activity for neurodegenerative diseasesRF1AG075055 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, JOHN W · 2022 to 2022
$1.5M
Collaborative Center for X-linked dystonia parkinsonism (CCXDP) at Massachusetts General HospitalEllison FoundationNIA NIH HHS R44 AG079734NIA NIH HHS RF1 AG075055NIH HHS R44AG079734NIH HHS RF1AG075055NINDS NIH HHS R01 NS102423
6 · The paper itself

Abstract

aimsAlthough the genetic locus of X-linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well-characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP.

methodsMPO activity was measured by using an MPO-activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP-derived fibroblasts and SH-SY5Y cells following MPO inhibition.

resultsMPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH-SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP-derived fibroblasts and XDP PFC-treated SH-SY5Y cells.

conclusionsCollectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.

Indexed as

Dystonic DisordersGenetic Diseases, X-LinkedPeroxidaseReactive Oxygen SpeciesCell Line, TumorFemaleFibroblastsHumansMaleMiddle AgedNeuroinflammatory DiseasesPiperidinesPrefrontal CortexMPO protein, humanPeroxidasePiperidinesReactive Oxygen SpeciesinflammationmyeloperoxidaseverdiperstatX‐linked dystonia parkinsonism

Identifiers

PMID39500625
PMCPMC11537767

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Registered trials

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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.