ArticleHaematologica2016
The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis).
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- LSD1 inhibition ameliorates congenital dyserythropoietic anemia type II.Science translational medicine · 2026Article
- Enhanced induction of fetal hemoglobin by the combination of decitabine with RN-1 in β-thalassemia/HbE erythroid progenitor cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Article
- Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.International journal of molecular sciences · 2024Review
- Combinatorial targeting of epigenome-modifying enzymes with decitabine and RN-1 synergistically increases HbF.Blood advances · 2023Article
- Review
- Effect of the LSD1 inhibitor RN-1 on γ-globin and global gene expression during erythroid differentiation in baboons (Papio anubis).PloS one · 2023Article
- Lysine-Specific Demethylase 1 (LSD1/KDM1A) Inhibition as a Target for Disease Modification in Myelofibrosis.Cells · 2022Review
- Perspectives and challenges to discovering hemoglobin-inducing agents in Sickle Cell Disease.Frontiers in medicine · 2022Article
- Article
- Lysine-specific histone demethylase 1 inhibition enhances robust fetal hemoglobin induction in human βHematology reports · 2021Article
- Article
- Exploring epigenetic and microRNA approaches for γ-globin gene regulation.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Discovery of DS79932728: A Potent, Orally Available G9a/GLP Inhibitor for Treating β-Thalassemia and Sickle Cell Disease.ACS medicinal chemistry letters · 2021Article
- Epigenetic regulation of hemoglobin switching in non-human primates.Seminars in hematology · 2021Review
- Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin.ChemMedChem · 2020Review
- Fetal hemoglobin in sickle cell anemia.Blood · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Increased fetal hemoglobin levels lessen the severity of symptoms and increase the lifespan of patients with sickle cell disease. Hydroxyurea, the only drug currently approved for the treatment of sickle cell disease, is not effective in a large proportion of patients and therefore new pharmacological agents that increase fetal hemoglobin levels have long been sought. Recent studies identifying LSD-1 as a repressor of γ-globin expression led to experiments demonstrating that the LSD-1 inhibitor RN-1 increased γ-globin expression in the sickle cell mouse model. Because the arrangement and developmental stage-specific expression pattern of the β-like globin genes is highly conserved between man and baboon, the baboon model remains the best predictor of activity of fetal hemoglobin-inducing agents in man. In this report, we demonstrate that RN-1 increases γ-globin synthesis, fetal hemoglobin, and F cells to high levels in both anemic and non-anemic baboons with activity comparable to decitabine, the most potent fetal hemoglobin-inducing agent known. RN-1 not only restores high levels of fetal hemoglobin but causes the individual 5' Iγ- and 3' Vγ-globin chains to be synthesized in the ratio characteristic of fetal development. Increased fetal hemoglobin was associated with increased levels of acetylated Histone H3, H3K4Me2, H3K4Me3, and RNA polymerase II at the γ-globin gene, and diminished γ-globin promoter DNA methylation. RN-1 is likely to induce clinically relevant levels of fetal hemoglobin in patients with sickle cell disease, although careful titration of the dose may be required to minimize myelotoxicity.
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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.