Sickle cell disease: Clinical presentation and management of a global health challenge

Houwing, Maite E.; Pagter, P.J. de; Beers, Eduard J. van; Biemond, Bart J.; Rettenbacher, Eva; Rijneveld, Anita W.; Schols, E.M.; Philipsen, Jacobus N. J.; Tamminga, R. Y. J.; Draat, Karin Fijn van; Nur, Erfan; Cnossen, Marjon H.

doi:10.1016/j.blre.2019.05.004

Cited by 59 publications

(75 citation statements)

References 402 publications

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“…Environmental factors (weather, air quality), fetal Hb levels, infections, and different genetic subtypes play a key role in exhibiting this disease. However, knowledge of the phenotypic expression of SCD is still limited [2,3].…”

mentioning

confidence: 99%

Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials

Ali

Ahmad

Chaudry

et al. 2020

Experimental Hematology

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MAA was responsible for conceptualization, methodology, and writing of the original draft. AA was responsible for visualization, supervision, and validation. HC was responsible for data curation, reviewing, and editing. WA was responsible for data curation and writing of the original draft. SA was responsible for data curation and writing of the original draft. MYA was responsible for data curation, writing, reviewing, editing, and software. AK was responsible for data curation and methodology.

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mentioning

confidence: 99%

Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials

Ali

Ahmad

Chaudry

et al. 2020

Experimental Hematology

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“…The molecular pathophysiology of these diseases, such as sickle cell disease, has been known for years, yet therapeutic options remain very limited. [1] Sickle cell disease is caused by a point mutation in the β-globin encoding gene HBB that causes the affected sickle hemoglobin (HbS) to polymerize under low-oxygen conditions. As a result, red blood cells become sickle-shaped and tend to block capillaries, which causes the accumulation of ischemic damage throughout the body.…”

Section: The Urgent Need To Develop Novel Drugs For β-Hemoglobinopathmentioning

confidence: 99%

“…[7] The level of HbF induction, however, varies among patients and thus the search continues for more potent and more specific compounds that derepress HbF. Repression of the HBG1/2 genes is well-studied, and many transcriptional regulators of the switch from HbF to HbA have been identified (see for instance supplementary Table 1 in Houwing et al [1] ). Epigenetic regulation facilitates and maintains the hemoglobin switch after birth, and provides avenues for drug development.…”

Section: The Urgent Need To Develop Novel Drugs For β-Hemoglobinopathmentioning

confidence: 99%

“…Recently, SPOP, one of the substrate adapters of the CUL3 ubiquitin ligase complex, was shown to be important for HbF repression. [1] Genetic knock-out of SPOP or CUL3 increased γglobin levels and slightly lowered BCL11A levels. [1]…”

Section: Molecular Regulation Of Hbf Repressionmentioning

confidence: 99%

“…[1] Genetic knock-out of SPOP or CUL3 increased γglobin levels and slightly lowered BCL11A levels. [1]…”

Section: Molecular Regulation Of Hbf Repressionmentioning

confidence: 99%

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Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin

et al. 2020

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The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β‐hemoglobinopathies in low‐income countries, therefore, calls for the development of affordable, off‐the‐shelf, oral treatments. The use of PROTAC (PRoteolysis TArgeting Chimeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity.

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