ArticleProceedings of the National Academy of Sciences of the United States of America2020
Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05166109 (A Phase II Pilot Trial of Vamorolone vs. Placebo for the Treatment of Becker Muscular Dystrophy), which is not on this map. Cited by 35 papers, 2 of them syntheses that pooled 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.
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.
A Phase II Pilot Trial of Vamorolone vs. Placebo for the Treatment of Becker Muscular Dystrophy
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Meta-analysis of the efficacy and safety of vamorolone in Duchenne muscular dystrophy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis.Frontiers in neurology · 2023Pooled it
- Prednisone, not vamorolone, suppresses novel serum bone and cartilage biomarkers associated with growth failure in children with Duchenne muscular dystrophy.Scientific reports · 2026Trial
- Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial.Neurology · 2026Trial
- Results of a phase II open-label, multiple-dose study of vamorolone (VBP15-006) in 7- to < 18-year-old boys with duchenne muscular dystrophy.Journal of neurology · 2026Trial
- Adrenal Suppression From Vamorolone and Prednisone in Duchenne Muscular Dystrophy: Results From the Phase 2b Clinical Trial.The Journal of clinical endocrinology and metabolism · 2025Trial
- Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial.JAMA network open · 2022Trial
- Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study.PLoS medicine · 2020Trial
- Adrenal Suppression in Duchenne Muscular Dystrophy: Management Strategies Incorporating Novel Steroid Vamorolone.Journal of the Endocrine Society · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- A structured approach to address variability in the global management of adrenal insufficiency in Duchenne muscular dystrophy: the 2025 PJ Nicholoff steroid protocol.Frontiers in neurology · 2026Review
- Post-marketing safety surveillance and signal characterization of the novel dissociative steroid Vamorolone in Duchenne muscular dystrophy: a comparative disproportionality analysis based on FAERS data.Frontiers in pharmacology · 2026Article
- Vamorolone: a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects.Rheumatology (Oxford, England) · 2025Article
- Impact of Replicas and Simulation Length on In Silico Behaviors of a Protein Domain.Chemphyschem : a European journal of chemical physics and physical chemistry · 2025Article
- Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.PNAS nexus · 2025Article
- Assessing Pharmacogenomic loci Associated with the Pharmacokinetics of Vamorolone in Boys with Duchenne Muscular Dystrophy.Journal of clinical pharmacology · 2024Article
- Ancient and modern mechanisms compete in progesterone receptor activation.RSC chemical biology · 2024Article
- Illuminating ligand-induced dynamics in nuclear receptors through MD simulations.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.Molecules (Basel, Switzerland) · 2024Article
- The mineralocorticoid receptor forms higher order oligomers upon DNA binding.Protein science : a publication of the Protein Society · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Duchenne muscular dystrophy is a genetic disorder that shows chronic and progressive damage to skeletal and cardiac muscle leading to premature death. Antiinflammatory corticosteroids targeting the glucocorticoid receptor (GR) are the current standard of care but drive adverse side effects such as deleterious bone loss. Through subtle modification to a steroidal backbone, a recently developed drug, vamorolone, appears to preserve beneficial efficacy but with significantly reduced side effects. We use combined structural, biophysical, and biochemical approaches to show that loss of a receptor-ligand hydrogen bond drives these remarkable therapeutic effects. Moreover, vamorolone uniformly weakens coactivator associations but not corepressor associations, implicating partial agonism as the main driver of its dissociative properties. Additionally, we identify a critical and evolutionarily conserved intramolecular network connecting the ligand to the coregulator binding surface. Interruption of this allosteric network by vamorolone selectively reduces GR-driven transactivation while leaving transrepression intact. Our results establish a mechanistic understanding of how vamorolone reduces side effects, guiding the future design of partial agonists as selective GR modulators with an improved therapeutic index.
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What OpenQuestion holds
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 OpenQuestion graph.