Evidence map›Paper›PMID 41430706›Full record

ArticleJournal of neuroinflammation2025

A systematic scoring system to optimise the testing of neurotherapeutics in models of perinatal brain injury, with an applied case study of human umbilical-cord MSC.

Cindy Bokobza, Clémence Réda, Syam Nair, David Guenoun, Eridan Rocha-Ferreira, Valérie Faivre, Tifenn Le Charpentier, Cora Nijboer, Caroline de Theije, Sophie Lebon and 14 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Cindy Bokobza *Université Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France. cindy.bokobza@inserm.fr.
Clémence Réda *Université Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Syam Nair *Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
David GuenounUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Eridan Rocha-FerreiraCentre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Valérie FaivreUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Tifenn Le CharpentierUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Cora NijboerDepartment for Developmental Origins of Disease, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Caroline de TheijeDepartment for Developmental Origins of Disease, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Sophie LebonUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Joakim EkCentre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Mohamed Gaeth HafezCentre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Leslie SchwendimannUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Médine BenchouaiaDépartement de Biologie, Genomique ENS, Institut de Biologie de L'ENS (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, 75005, France.
Sophie LemoineDépartement de Biologie, Genomique ENS, Institut de Biologie de L'ENS (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, 75005, France.
Giorgia VolpiGlobal Rare Diseases, Chiesi Farmaceutici S.P.A., Parma, 43122, Italy.
Katiuscia DallaglioGlobal Rare Diseases, Chiesi Farmaceutici S.P.A., Parma, 43122, Italy.
Nicola PelizziGlobal R&D, Chiesi Farmaceutici S.P.A., Parma, 43122, Italy.
Bobbi FleissUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France. bobbi.fleiss@rmit.edu.au.
Juliette Van SteenwinckelUniversité Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Andrée Delahaye-Duriez *Université Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
Henrik Hagberg *Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Pierre Gressens *Université Paris Cité, NeuroDiderot, Inserm, Paris, 75019, France.
PREMSTEM consortium

Funding

European Union 874721/PREMSTEM
6 · The paper itself

Abstract

The preclinical stages of therapeutic agent development cost hundreds of millions of dollars, stymying innovation and slowing the development of products to improve human health. There is a striking unmet need for therapies that protect or repair the brain damage associated with preterm birth, i.e., delivery before 37 weeks of gestation. Of the more than 15 million babies born preterm every year, up to 60% will go on to develop a neurological disorder, with the earliest-born infants the most impacted. We have limited options with limited efficacy for preventing or treating these changes. Combining accurate knowledge of pathophysiology with high-throughput sequencing and computational biology approaches is a logical step towards an optimised screening pipeline. In this study, we conducted comprehensive testing of dose, timing, and route of administration, integrating multimodal data from preclinical models of brain injury common in preterm-born infants to validate the most effective therapeutic option for the cord-derived mesenchymal stem cell product (HuMSC). In this study, HuMSC serves as a working example, but the scoring system is therapy-agnostic. We developed a scoring protocol based on microglia transcriptome analyses and myelin protein expression to evaluate the efficacy of the HuMSC product in a rat model of inflammation-associated preterm infant brain injury. We identified the superiority of treatment delivered in the tertiary phase of injury over treatments in the acute or subacute stages, as well as the superiority of intranasal over intravenous delivery of HuMSCs. The optimal time, dose, and route of administration options for HuMSC were confirmed in a second model relevant to preterm infants, but with a different pathophysiology, namely germinal matrix haemorrhage. In conclusion, we have established a scoring protocol that expedites the collection of comprehensive dose, time and route of administration data critical for establishing large animal and clinical trials with the greatest chance of success.

Indexed as

Brain InjuriesMesenchymal Stem CellsMesenchymal Stem Cell TransplantationUmbilical CordAnimalsAnimals, NewbornDisease Models, AnimalFemaleHumansInfant, NewbornLipopolysaccharidesMicrogliaPregnancyRatsRats, Sprague-DawleyLipopolysaccharidesAutomated outcome scoringEncephalopathy of prematurityMicrogliaMyelinationNeuroinflammationPathway analysisPhenotype rescueStem cell therapy

Identifiers

PMID41430706
PMCPMC12772108

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.