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Record W1508659364 · doi:10.1002/mus.24332

Ataluren treatment of patients with nonsense mutation dystrophinopathy

2014· article· en· W1508659364 on OpenAlexaff
K. Bushby, Richard S. Finkel, Brenda Wong, Richard J. Barohn, Craig Campbell, Giacomo P. Comi, Anne M. Connolly, Kevin M. Flanigan, Nathalie Goemans, Kristi Jones, Eugenio Mercuri, Rosaline C. M. Quinlivan, J. Ben Renfroe, Barry S. Russman, Monique M. Ryan, M. Tulinius, Thomas Voït, Steven A. Moore, H. Lee Sweeney, Richard T. Abresch, Kim L. Coleman, Michelle Eagle, Julaine Florence, Eduard Gappmaier, Allan M. Glanzman, Erik Henricson, Jay Barth, Gary Elfring, A. Reha, Robert J. Spiegel, Michael W. O'donnell, Stuart W. Peltz, Craig M. McDonald

Bibliographic record

VenueMuscle & Nerve · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsWestern University
FundersNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeMedical Research CouncilMuscular Dystrophy UKPTC TherapeuticsNationwide Children's HospitalChildren's Hospital of PhiladelphiaNational Institute for Health and Care ResearchMuscular Dystrophy Association
KeywordsNonsense mutationMedicinePlaceboDuchenne muscular dystrophyClinical endpointInternal medicinePediatricsSurgeryClinical trialMutationGeneticsBiologyPathologyMissense mutation

Abstract

fetched live from OpenAlex

INTRODUCTION: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. METHODS: Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. RESULTS: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. CONCLUSIONS: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.200
Teacher spread0.196 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations426
Published2014
Admission routes1
Has abstractyes

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