Evidence map›Paper›PMID 30514970›Full record

ReviewNature reviews. Drug discovery2019

Therapeutic strategies for sickle cell disease: towards a multi-agent approach.

Marilyn J Telen, Punam Malik, Gregory M Vercellotti

Open access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Drug discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.

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  4. bioRxiv : the preprint server for biology · 2026
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 3 institutions in 1 country.

Marilyn J TelenDivision of Hematology, Department of Medicine and Duke Comprehensive Sickle Cell Center, Duke University, Durham, NC, USA. marilyn.telen@duke.edu.
Punam MalikDivision of Experimental Hematology and Cancer Biology and the Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Gregory M VercellottiDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Cincinnati Children's Hospital Medical Center · USDuke University · USUniversity of Minnesota · US

Funding

Cincinnati Center of Excellence in Hemoglobinopathies ResearchU01HL117709 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI MALIK, PUNAM · 2013 to 2017
$8.9M
Heme toxicity and vaso-occlusion in sickle cell diseaseR01HL114567 · NHLBI · UNIVERSITY OF MINNESOTA · PI VERCELLOTTI, GREGORY M · 2012 to 2020
$4.4M
Hemostatic factors and sickle cell diseaseR01HL112603 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI FLICK, MATTHEW J., MALIK, PUNAM · 2012 to 2016
$1.9M
Factor XIII and Fibrinogen: Mechanisms of Genetic Risk in SCD-Related PriapismR21DK106509 · NIDDK · DUKE UNIVERSITY · PI TELEN, MARILYN J · 2015 to 2016
$445k
NHLBI NIH HHS R01 HL112603NHLBI NIH HHS R01 HL114567NHLBI NIH HHS U01 HL117709NIDDK NIH HHS R21 DK106509
6 · The paper itself

Abstract

For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlusion, anaemia, haemolysis, organ injury and pain. However, despite growing understanding of the mechanisms of haemoglobin S polymerization and its effects on red blood cells, only two therapies for SCD - hydroxyurea and L-glutamine - are approved by the US Food and Drug Administration. Moreover, these treatment options do not fully address the manifestations of SCD, which arise from a complex network of interdependent pathophysiological processes. In this article, we review efforts to develop new drugs targeting these processes, including agents that reactivate fetal haemoglobin, anti-sickling agents, anti-adhesion agents, modulators of ischaemia-reperfusion and oxidative stress, agents that counteract free haemoglobin and haem, anti-inflammatory agents, anti-thrombotic agents and anti-platelet agents. We also discuss gene therapy, which holds promise of a cure, although its widespread application is currently limited by technical challenges and the expense of treatment. We thus propose that developing systems-oriented multi-agent strategies on the basis of SCD pathophysiology is needed to improve the quality of life and survival of people with SCD.

Indexed as

Drug Therapy, CombinationAnemia, Sickle CellAnimalsAntisickling AgentsDrug Delivery SystemsGenetic TherapyHumansAntisickling Agents

Identifiers

PMID30514970
PMCPMC6645400
OpenAlexW2902685885

What OpenQuestion holds

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Registered trials

None linked

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.