Emerging drugs for sickle cell anemia

Singh, Priya C; Ballas, Samir K.

doi:10.1517/14728214.2015.985587

Cited by 18 publications

(13 citation statements)

References 78 publications

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“…However, preclinical developments and early trials have already been extensively discussed in other reviews. [25][26][27] In this review, we aimed to focus on interventions in advanced stages of evaluation that are closer to clinical implementation.…”

Section: Discussionmentioning

confidence: 99%

“…Encouragingly, the number of clinical trials in SCD has increased recently, and many novel therapies are currently under investigation. [25][26][27] …”

Section: Discussionmentioning

confidence: 99%

“…Many are currently under investigation in preclinical or early-phase trials, as extensively discussed in other reviews. [25][26][27] However, some treatments have already been evaluated in phase 2 or 3 randomized clinical trials (RCTs), but a clear overview of these studies and their findings does not exist. The objective of this study was to systematically review the currently available controlled clinical trials, investigating new pharmacotherapeutical strategies in the prevention of VOCs in SCD.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

et al. 2017

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Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs).Various treatments have been evaluated over the years. However, a clear overview is lacking.The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD.Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants L-glutamine and v-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was

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Section: Discussionmentioning

confidence: 99%

“…Encouragingly, the number of clinical trials in SCD has increased recently, and many novel therapies are currently under investigation. [25][26][27] …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

et al. 2017

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“…sickle cell | drugs | hemoglobin S | treatment | screening assay T here is currently only one specific drug being used to treat sickle cell disease (1)(2)(3), despite the fact that a therapeutic target has been known since Pauling's discovery in 1949 that a mutation of the hemoglobin molecule is responsible (4). Sickle hemoglobin (HbS) polymerizes upon deoxygenation to form fibers that stiffen and distort ("sickle") the red cells.…”

mentioning

confidence: 99%

Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease

Henry

Hofrichter

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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.sickle cell | drugs | hemoglobin S | treatment | screening assay

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“…Such trials will determine if a certain drug is safe, efficacious, and capable of improving the quality of life of treated patients. Recently, Singh and Ballas reviewed about 38 drugs that were tried or about to be tried in several clinical trials for the prevention of VOCs and related complications [153]. As mentioned above, the Phase III trial of senicapoc was terminated because patients who took senicapoc had more VOCs than control subjects.…”

Section: Other Novel Approaches To Therapymentioning

confidence: 99%

Sickle cell disease: Classification of clinical complications and approaches to preventive and therapeutic management

Ballas

2018

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Emerging drugs for sickle cell anemia

Cited by 18 publications

References 78 publications

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease

Sickle cell disease: Classification of clinical complications and approaches to preventive and therapeutic management

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