Evidence map›Paper›PMID 38942888›Full record

ArticlePediatric research2024

Minimum effective dose of clemastine in a mouse model of preterm white matter injury.

Elizabeth P Odell, Nora Jabassini, Björn Schniedewind, Sarah E Pease-Raissi, Adam Frymoyer, Uwe Christians, Ari J Green, Jonah R Chan, Bridget E L Ostrem

Abstract read
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In one paragraph

Article in Pediatric research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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  4. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Elizabeth P OdellWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Nora JabassiniWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Björn SchniedewindiC42 Clinical Research and Development, Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Sarah E Pease-RaissiWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Adam FrymoyerDepartment of Pediatrics, Stanford University, Palo Alto, CA, USA.
Uwe ChristiansiC42 Clinical Research and Development, Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ari J GreenWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Jonah R ChanWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Bridget E L OstremWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. bridget.ostrem@ucsf.edu.

Funding

Child Neurologist Career Development Program (CNCDP)K12NS098482 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI SCHLAGGAR, BRADLEY L · 2016 to 2025
$26.2M
NINDS NIH HHS K12 NS098482
6 · The paper itself

Abstract

backgroundPreterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the myelinating cells of the central nervous system. Clemastine was previously shown to induce oligodendrocyte differentiation and myelination in mouse models of PWMI at a dose of 10 mg/kg/day. The minimum effective dose (MED) of clemastine is unknown. Identification of the MED is essential for maximizing safety and efficacy in neonatal clinical trials. We hypothesized that the MED in neonatal mice is lower than 10 mg/kg/day.

methodsMouse pups were exposed to normoxia or hypoxia (10% FiO2) from postnatal day 3 (P3) through P10. Vehicle or clemastine at one of four doses (0.5, 2, 7.5 or 10 mg/kg/day) was given to hypoxia-exposed pups. Myelination was assessed at age P14 and 10 weeks to determine the MED. Clemastine pharmacokinetics were evaluated at steady-state on day 8 of treatment.

resultsClemastine rescued hypoxia-induced hypomyelination with a MED of 7.5 mg/kg/day. Pharmacokinetic analysis of the MED revealed C

conclusionsBased on these results, myelination-promoting exposures should be achievable with oral doses of clemastine in neonates with PWMI. IMPACT: Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates. Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment. The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials. We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.

Indexed as

Animals, NewbornClemastineDisease Models, AnimalWhite MatterAnimalsDose-Response Relationship, DrugFemaleHumansHypoxiaMiceMice, Inbred C57BLMyelin SheathOligodendrogliaClemastine

Identifiers

PMID38942888
PMCPMC11502491

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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.