Pharmacogenomics of the Drugs used for the Treatment of Thalassemia

Panja, Amrita; Basu, Anupam

doi:10.4172/2157-7099.1000360

Cited by 3 publications

(3 citation statements)

References 25 publications

(22 reference statements)

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“…Butyrates are a class of histone deacetylase (HDAC) inhibitors demonstrated to be able to increase γ-globin gene expression and HbF content in erythroid cells from βthalassemic and SCD patients [171][172][173]. It has been reported that at least 25% of the patients affected by hemoglobinopathies do not respond to treatment with butyrates [174,175]. However, despite the fact that butyrates have been proposed as good candidate drugs for pharmacogenomic studies [174], few reports have been published on this issue.…”

Section: Butyrate and Butyrate Analoguesmentioning

confidence: 99%

“…It has been reported that at least 25% of the patients affected by hemoglobinopathies do not respond to treatment with butyrates [174,175]. However, despite the fact that butyrates have been proposed as good candidate drugs for pharmacogenomic studies [174], few reports have been published on this issue. An interesting study is based on the observation that patients who are unresponsive to HU treatment can be treated with sodium butyrate containing microRNAs to induce HbF synthesis [174,176].…”

Section: Butyrate and Butyrate Analoguesmentioning

confidence: 99%

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Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

Gambari,

Waziri,

Goonasekera

et al. 2024

IJMS

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In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the HBG2 XmnI polymorphism and those related to the BCL11A, MYB, KLF-1, and LYAR genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.

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Section: Butyrate and Butyrate Analoguesmentioning

confidence: 99%

Section: Butyrate and Butyrate Analoguesmentioning

confidence: 99%

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

Gambari,

Waziri,

Goonasekera

et al. 2024

IJMS

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“…The effectiveness of HU administration was reported only in certain groups of patients with β thalassemia major, because it requires selecting groups of responders and nonresponders. Several studies have even reported failure of HU therapy in patients with β-thalassemia major (Dreuzy et al, 2016;Panja & Basu, 2015;Thein, 2005).…”

Section: Introductionmentioning

confidence: 99%

EFFECT OF Anti-miRNA 144 AND Anti-miRNA 150 ON THE EXPRESSION OF α GLOBIN CHAINS IN PBMC

Riyanti¹

2022

JSCRTE

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The excess of unbound α globin chains are the basic pathophysiology of the cause of clinical symptoms in major β thalassemia. Recently there are many alternative therapies by increasing γ globin chains to reduced the effects of unbound α globin chains. Alternative therapies by decreasing α globin chains have not been much noticed. α globin expression involves complex regulatory involving transcription factors and miRNAs. It involves GATA-1, KLFD and MYB transcription factors . It also involves miRNA-144 and miRNA-150. The role of miRNA-144 and miRNA-150 to reduce the α globin chains expression in major β thalassemia patients is an alternative therapy. miRNA-144 and miRNA150 activity need to be known by using anti-miRNA 144 and anti- miRNA 150. Analyzed the effect of anti-miRNA 144 and anti-miRNA 150 on the expression of α globin chains. This study was an experimental study using PBMC of a major β thalassemia patients. PBMC divided into four groups that were not transfected, transfected by anti-miRNA 144, transfected by anti-miRNA 150 and transfected by anti-miRNA 144 and anti-miRNA 150. qPCR examinations to find out expression of miRNA-144 and miRNA-150. Western blot examination to find out the expression of α globin chains. There was significantly lower miRNA-144 expression in PBMC of major β thalassemia patients who had been transfected by anti-miRNA 144 than those not transfected. In line with the result of miRNA-144 expression which was 0.17 times lower than the control group. There was significantly lower miRNA-150 expression in PBMC of major β thalassemia patients who had been transfected by anti-miRNA 150 than those not transfected. In line with the result of miRNA-150 expression which was 0.30 times lower than the control group. There was significantly lower α globin chains expression in PBMC thalassemia patients who had been transfected by anti-miRNA 150 than those not transfected. There was significantly lower α globin chains expression in PBMC thalassemia patients who had been transfected by anti-miRNA 150 and anti-miRNA 144 than those not transfected. This is evidenced by the decreased in the area 10-25 KDa band. Based on this study, the administration of anti-miRNA 150 or anti-miRNA 144 and anti-miRNA 150 is capable of decreasing the expression α globin chains in PBMC of major β thalassemia patients.

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Molecular Docking of Andrographoilde and HDAC2 inhibitor an approach to manage for Beta Thalassemia

Khare,

Chatterjee,

Gupta

et al. 2023

RJPT

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Beta thalassemia is a disorder of globin gene synthesis resulting in the absent production of beta globin chain in RBC. The property of inducing gamma globin gene expression by the search for bioactive compounds exhibiting is of great interest. Regulation of HDAC activity by dietary flavones couldhave important implication in developing epigenetic therapy to regulate the cell geneexpression. Several pharmacological agents have been identified overthe past two decades that reactivate gamma globin gene transcription through differentcellular system. We will search for the complementary and alternative medicine (CAM)which regulated switch from fetal to adult globin gene expression could be prevented hasresult in the development of new class of therapeutic agent consisting of some bioactivecompounds such as flavanone for the treatment of beta thalassemia. Flavones one suchmolecule of plant origin are known to interfere with HDAC2 enzyme and to enhance theacetylation restoring cell homeostasis, p38 MAPK pathway. Induction of HbF expression inerythroid cells is an important and another therapeutic approach in beta thalassemia. We used Schrodinger suites to develop computational approaches for estimating drug and target binding affinities. The target enzyme's sequence alignments contain 539 amino acid residues, and bioactive compounds that act as ligand molecules were acquired from the plant Andrographis paniculata. We used molecular docking, and ADME analysis. The current study explores the binding pattern of Andrographoilde and Vorinostat (SAHA) against their target protein (PDBIDs: 6G3O), respectively using molecular docking approaches. The molecular docking results show that Andrographoilde binds within the active region of HDAC2 inhibitors by forming hydrogen bonds against ASP104 and TYR 308 respectively. However, the Vorinostat interacts with TYR 308 and GLY 142respectively. Our comparative results show that andrographoilde may be a similar therapeutic agent for managing beta thalassemia as compare to vorinostat. However, functional studies are needed to confirm their proposed relevance in beta thalassemia in vitro and in vivo evaluation studies are required.

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Pharmacogenomics of the Drugs used for the Treatment of Thalassemia

Cited by 3 publications

References 25 publications

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

EFFECT OF Anti-miRNA 144 AND Anti-miRNA 150 ON THE EXPRESSION OF α GLOBIN CHAINS IN PBMC

Molecular Docking of Andrographoilde and HDAC2 inhibitor an approach to manage for Beta Thalassemia

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