ArticleProceedings of the National Academy of Sciences of the United States of America2017
Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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
30 citing papers in PubMed, 46 citations in OpenAlex.
- In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.Blood advances · 2024Trial
- Endothelin receptor antagonism in sickle cell disease: Is the time now?Canadian journal of physiology and pharmacology · 2026Review
- In Silico Post-screening of Anti-polymerization Agents to Treat Sickle Cell Disease.bioRxiv : the preprint server for biology · 2025Article
- Article
- Hope on the Horizon: New and Future Therapies for Sickle Cell Disease.Journal of clinical medicine · 2023Review
- Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation.Biophysical journal · 2023Article
- Screen "play" for drug discovery.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Fluorescence Lifetime Measurement of Prefibrillar Sickle Hemoglobin Oligomers as a Platform for Drug Discovery in Sickle Cell Disease.Biomacromolecules · 2022Article
- The erythroid K-Cl cotransport inhibitor [(dihydroindenyl)oxy]acetic acid blocks erythroid CaAmerican journal of physiology. Cell physiology · 2022Article
- Ionophore-mediated swelling of erythrocytes as a therapeutic mechanism in sickle cell disease.Haematologica · 2022Article
- High-Throughput Assay to Screen Small Molecules for Their Ability to Prevent Sickling of Red Blood Cells.ACS omega · 2022Article
- Impact of hemoglobin biophysical studies on molecular pathogenesis and drug therapy for sickle cell disease.Molecular aspects of medicine · 2022Review
- GBT1118, a voxelotor analog, protects red blood cells from damage during severe hypoxia.American journal of translational research · 2022Article
- Drug discovery by a basic research scientist.Frontiers in molecular biosciences · 2022Article
- Article
- MWC allosteric model explains unusual hemoglobin-oxygen binding curves from sickle cell drug binding.Biophysical journal · 2021Article
- Rational Drug Design of Peptide-Based Therapies for Sickle Cell Disease.Molecules (Basel, Switzerland) · 2019Review
- High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Quantitative prediction of erythrocyte sickling for the development of advanced sickle cell therapies.Science advances · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Although it has been known for more than 60 years that the cause of sickle cell disease is polymerization of a hemoglobin mutant, hydroxyurea is the only drug approved for treatment by the US Food and Drug Administration. This drug, however, is only partially successful, and the discovery of additional drugs that inhibit fiber formation has been hampered by the lack of a sensitive and quantitative cellular assay. Here, we describe such a method in a 96-well plate format that is based on laser-induced polymerization in sickle trait cells and robust, automated image analysis to detect the precise time at which fibers distort ("sickle") the cells. With this kinetic method, we show that small increases in cell volume to reduce the hemoglobin concentration can result in therapeutic increases in the delay time prior to fiber formation. We also show that, of the two drugs (AES103 and GBT440) in clinical trials that inhibit polymerization by increasing oxygen affinity, one of them (GBT440) also inhibits sickling in the absence of oxygen by two additional mechanisms.
Indexed as
Identifiers
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.