l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope?

Leibovitch, Jennifer; Tambe, Ajay; Cimpeanu, Emanuela; Poplawska, Maria; Jafri, Firas; Dutta, Dibyendu; Lim, Seah H.

doi:10.1016/j.blre.2021.100925

Cited by 26 publications

(26 citation statements)

References 64 publications

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“…The newer agents available for the treatment of sickle cell anemia include L-glutamine, crizanlizumab, and voxelotor. These drugs are beneficial in increasing the hemoglobin concentration or decreasing the frequency of VOCs, which may indirectly reduce the frequency of ACS [ 22 ]. However, there has been no proven benefit reported that these drugs may directly reduce the frequency of ACS [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…These drugs are beneficial in increasing the hemoglobin concentration or decreasing the frequency of VOCs, which may indirectly reduce the frequency of ACS [ 22 ]. However, there has been no proven benefit reported that these drugs may directly reduce the frequency of ACS [ 22 ]. Hematopoietic stem cell transplantation (HSCT) provides curative therapy for children with SCD, as it eradicates acute complications and prevents further end-organ damage [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Predictors of Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: A Retrospective Case-Control Study

et al. 2022

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Acute chest syndrome (ACS) is a common cause of death in sickle cell disease (SCD) patients. Multiple studies investigated the risk factors of developing ACS; however, predictors of recurrent ACS episodes have not been thoroughly investigated. We aim to examine the clinical and laboratory predictors of recurrent ACS in pediatric patients with SCD. A retrospective case-control study included pediatric patients with SCD (˂14 years) admitted with ACS or developed ACS during admission for another indication. Patients were classified into recurrent ACS episodes (≥2 episodes) and a single ACS episode groups. Ninety-one ACS episodes (42 patients) were included, with a mean age at diagnosis of 7.18 ± 3.38 years. Twenty-two (52.4%) patients were male, and twenty-five (59.5%) patients had recurrent ACS. Younger age at first ACS was significantly associated with recurrence (p = 0.003), with an optimal cutoff at 7.5 years (area under the receiver operating characteristic curve [AUROC] = 0.833; p < 0.001). Higher SCD-related hospitalizations were significantly associated with recurrence (p = 0.038). Higher mean values of baseline white blood count (WBC) (p = 0.009), mean corpuscular volume (MCV) (p = 0.011), and reticulocyte (p = 0.036) were significantly associated with recurrence. Contrarily, lower baseline hematocrit values (p = 0.016) were significantly associated with recurrence. The ACS frequencies were significantly lower after hydroxyurea (p = 0.021). The odds of ACS recurrence increased with a positive C-reactive protein (CRP) at admission (p = 0.006). In conclusion, several baseline and admission laboratory data showed significant associations with recurrence. Hydroxyurea therapy demonstrated reduced ACS episodes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Predictors of Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: A Retrospective Case-Control Study

et al. 2022

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“…The table below shows representative compounds tested for BPGM inhibition, including the biological data obtained from testing representative examples. …”

Section: Important Compound Classesmentioning

confidence: 99%

Novel Bis-phosphoglycerate Mutase Modulators for Treating Sickle Cell Disease

Sabnis¹

2022

ACS Med. Chem. Lett.

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Assignee Company. Genzyme Corporation, USA Disease Area. Sickle cell disease Biological Target. Bis-phosphoglycerate mutase Summary. Bis-phosphoglycerate mutase (BPGM) is an enzyme in the glucose metabolism pathway that regulates the levels of 2,3-bis-phosphoglycerate (2,3-BPG) inside the red blood cell (RBC). 2,3-BPG is a known allosteric modulator of hemoglobin that stabilizes the deoxy or "T-state" of hemoglobin that has a tendency to polymerize, resulting in the sickle cell morphology. BPGM modulators that lower 2,3-BPG levels offer a novel mechanism of action from existing therapies and may significantly reduce sickling in sickle cell disease patients.The present application describes a series of novel bisphosphoglycerate mutase compounds as modulators for the treatment of sickle cell disease. Further, the application discloses compounds, their preparation, use, and pharmaceutical composition, and treatment.

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“…Allogeneic hematopoietic stem cell transplant (allo-HSCT), the curative approach for SCA, could be applied to a small number of patients since about only 20% of them have a healthy HLA-identical sibling donor ( 6 ). In addition, the high cost, which was valued in the US estimate at $406,193, chronic graft vs. host disease, and high rates of morbidities made such an approach difficult in the clinical routine ( 7 ). Genetically modified autologous stem cells were an alternative for curing that included correcting the mutation associated with the disease through gene editing (i.e., CRISPR-Cas9), restoring HbF production by knockout transcription factors such as BCL11A, or including modified β-globin genes that avoid hemoglobin polymerization (i.e., LentiGlobin BB305) ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the high cost, which was valued in the US estimate at $406,193, chronic graft vs. host disease, and high rates of morbidities made such an approach difficult in the clinical routine ( 7 ). Genetically modified autologous stem cells were an alternative for curing that included correcting the mutation associated with the disease through gene editing (i.e., CRISPR-Cas9), restoring HbF production by knockout transcription factors such as BCL11A, or including modified β-globin genes that avoid hemoglobin polymerization (i.e., LentiGlobin BB305) ( 7 , 8 ). The cost for gene therapy was estimated to be above 1 million USD ( 6 ), and access to this strategy was limited, but in the long run, gene therapy could be a safer alternative than allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

Perspectives and challenges to discovering hemoglobin-inducing agents in Sickle Cell Disease

Pavan

Lopes

Imperador³

et al. 2022

Front. Med.

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l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope?

Cited by 26 publications

References 64 publications

Predictors of Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: A Retrospective Case-Control Study

Predictors of Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: A Retrospective Case-Control Study

Novel Bis-phosphoglycerate Mutase Modulators for Treating Sickle Cell Disease

Perspectives and challenges to discovering hemoglobin-inducing agents in Sickle Cell Disease

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