Trial reportAnnals of neurology2014
Epigenetic therapy for Friedreich ataxia.
Trial report in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Therapeutic Biomarkers in Friedreich's Ataxia: a Systematic Review and Meta-analysis.Cerebellum (London, England) · 2024Pooled it
- Pharmacological treatments for Friedreich ataxia.The Cochrane database of systematic reviews · 2016Pooled it
- Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.Neurology · 2025Trial
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.The Journal of clinical investigation · 2026Article
- Advances in Gene and Cellular Therapy in Friedreich Ataxia.Molecular diagnosis & therapy · 2026Review
- BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin.Nature cell biology · 2026Article
- Evolution of Friedreich's Ataxia Management Across Established and Emerging Therapies-Systematic Review and Meta-Analysis.Journal of clinical medicine · 2026Review
- FXN protomutations are the source of pathogenic expanded GAA alleles in Friedreich ataxia and explain its unequal population distribution.Human molecular genetics · 2026Article
- Human pluripotent stem cell models of Friedreich's ataxia: innovations, considerations, and future perspectives.Stem cell research & therapy · 2026Review
- Recent developments in Friedreich's ataxia: a state-of-the-art review.Brain communications · 2026Review
- Histone Deacetylases in Neurodegenerative Diseases and Their Potential Role as Therapeutic Targets: Shedding Light on Astrocytes.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Anti-gene oligonucleotides targeting Friedreich's ataxia expanded GAA⋅TTC repeats increase Frataxin expression.Molecular therapy. Nucleic acids · 2025Article
- A global perspective on research advances and future challenges in Friedreich ataxia.Nature reviews. Neurology · 2025Review
- Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery.Neurology. Genetics · 2025Article
- Review
- Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich's ataxia iPSC-derived neurons.Frontiers in pharmacology · 2024Article
- The occurrence and development of induced pluripotent stem cells.Frontiers in genetics · 2024Review
- Patient-derived iPSC models of Friedreich ataxia: a new frontier for understanding disease mechanisms and therapeutic application.Translational neurodegeneration · 2023Review
- Interferon Gamma Enhances Cytoprotective Pathways via Nrf2 and MnSOD Induction in Friedreich's Ataxia Cells.International journal of molecular sciences · 2023Article
- Friedreich ataxia: clinical features and new developments.Neurodegenerative disease management · 2022Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
objectiveTo investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients.
methodsWe used a human FRDA neuronal cell model, derived from patient induced pluripotent stem cells, to determine the efficacy of a 2-aminobenzamide HDACi (109) as a modulator of FXN gene expression and chromatin histone modifications. FRDA patients were dosed in 4 cohorts, ranging from 30mg/day to 240mg/day of the formulated drug product of HDACi 109, RG2833. Patients were monitored for adverse effects as well as for increases in FXN mRNA, frataxin protein, and chromatin modification in blood cells.
resultsIn the neuronal cell model, HDACi 109/RG2833 increases FXN mRNA levels and frataxin protein, with concomitant changes in the epigenetic state of the gene. Chromatin signatures indicate that histone H3 lysine 9 is a key residue for gene silencing through methylation and reactivation through acetylation, mediated by the HDACi. Drug treatment in FRDA patients demonstrated increased FXN mRNA and H3 lysine 9 acetylation in peripheral blood mononuclear cells. No safety issues were encountered.
interpretationDrug exposure inducing epigenetic changes in neurons in vitro is comparable to the exposure required in patients to see epigenetic changes in circulating lymphoid cells and increases in gene expression. These findings provide a proof of concept for the development of an epigenetic therapy for this fatal neurological disease.
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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.