Evidence map›Paper›PMID 39793573›Full record

Trial reportCell reports. Medicine2025

Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy.

Hirofumi Komaki, Eri Takeshita, Katsuhiko Kunitake, Takami Ishizuka, Yuko Shimizu-Motohashi, Akihiko Ishiyama, Masayuki Sasaki, Chihiro Yonee, Shinsuke Maruyama, Eisuke Hida and 1 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04129294 (Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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.

NCT04129294 phase1 / phase2completednot on this map

Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy

TypeinterventionalSponsorNational Center of Neurology and Psychiatry, JapanRan2019 to 2022Enrolled6ConditionsDuchenne Muscular DystrophyArmsNS-089/NCNP-02
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Antisense RNA therapies for muscular dystrophies.Journal of neuromuscular diseases · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Serum protein biomarker signature of Duchenne muscular dystrophy.European journal of translational myology · 2025
    Article
  10. Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  11. Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2025
    Review
  12. Review
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

11 authors.

Hirofumi KomakiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8551, Japan; Translational Medical Center, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan.
Eri TakeshitaDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8551, Japan.
Katsuhiko KunitakeDepartment of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan.
Takami IshizukaTranslational Medical Center, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan.
Yuko Shimizu-MotohashiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8551, Japan.
Akihiko IshiyamaDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8551, Japan.
Masayuki SasakiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8551, Japan.
Chihiro YoneeDepartment of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Kagoshima 890-8520, Japan.
Shinsuke MaruyamaDepartment of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Kagoshima 890-8520, Japan.
Eisuke HidaDepartment of Biostatistics and Data Science, Graduate School of Medicine, Osaka University, Suita-Shi, Osaka 565-0871, Japan.
Yoshitsugu AokiDepartment of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan. Electronic address: tsugu56@ncnp.go.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers. An open-label, dose-escalation, phase 1/2 trial assessed the safety, pharmacokinetics, and efficacy of brogidirsen in six ambulant patients with DMD amenable to exon 44 skipping. Following dose escalation, extended 24-week treatment with 40 mg/kg and 80 mg/kg yielded dose-dependent increases in dystrophin (16.63% and 24.47% of normal). Functional assessments indicated motor stabilization, and plasma proteomics revealed reductions in peptidyl arginine deiminase 2 (PADI2), titin (TTN), and myomesin 2 (MYOM2), highlighting potential biomarkers. Brogidirsen's efficacy was supported in vitro using urine-derived cells from patients with DMD. These promising results warrant a subsequent trial for DMD. This study was registered at ClinicalTrials.gov (NCT04129294).

Indexed as

ExonsMuscular Dystrophy, DuchenneOligonucleotides, AntisenseAdolescentChildDystrophinHumansMaleMorpholinosDystrophinMorpholinosOligonucleotides, Antisenseantisense oligonucleotidesDMDdual targetingDuchennedystrophinexon 44exon skippingmorpholinoplasma proteomicsurine-derived cells

Identifiers

PMID39793573
PMCPMC11866436

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.