Ignite Creation Date:
2024-05-06 @ 7:05 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05883254
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-05-31
First Post:
2023-05-21
Brief Title:
Pumilio1 PUM1 Expression Sickle Cell Anemia β-thalassemia Intermedia
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Detection of RNA Binding Protein Pumilio1 PUM1 Expression in Patients With Sickle Cell Anemia and β-thalassemia Intermedia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 To study the expression pattern of PUM1 gene in patients with sickle cell anemia and β-thalassemia intermedia
2 To detect PUM1 protein levels in sickle cell anemia and β-thalassemia intermedia patients
3 To correlate PUM1 gene expression pattern and protein levels with HbF levels in sickle cell anemia and β-thalassemia intermedia patients
2 To detect PUM1 protein levels in sickle cell anemia and β-thalassemia intermedia patients
3 To correlate PUM1 gene expression pattern and protein levels with HbF levels in sickle cell anemia and β-thalassemia intermedia patients
Detailed Description:
The disorders of β-hemoglobin sickle cell disease SCD and β-thalassemia are major causes of morbidity and mortality worldwide These diseases are the most common genetic disorders in the world
SCD is due to a single base-pair point mutation in the β-globin gene resulting in the substitution of valine for glutamic acid in the β-globin chain The pathophysiology is directly related to polymerization of deoxygenated hemoglobin leading to a cascade of pathologic events including erythrocyte sickling vaso-occlusion and hemolysis
In β-thalassemia insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells As a result a significant anemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs
The hemoglobin molecule is a tetramer composed of two subunits of α-like globin peptides and two subunits of the β-like globin peptides along with heme moieties β-globin switching from fetal γ-globin HBG1 and HBG2 to adult β-globin is a developmental process that occurs in erythrocytes at around the time of birth Fetal hemoglobin HbF induction in adult erythrocytes is an effective therapeutic strategy for SCD and β-thalassemia
Pumilio1 PUM1 is a novel target of the erythroid master transcription factor erythroid Krüppel-like factor EKLF PUM1 is a member of Pumilio-Fem3-binding factor PUF family of sequence specific RNA-binding proteins acts as a posttranscriptional repressor by binding to the 3 untranslated region 3-UTR of messenger RNA mRNA It peaks during terminal erythroid differentiation and binds to fetal γ-globin HBG1 mRNA and impairs its stability and translation HBG1 has 2 core PUM1 consensus binding sites but HBG2 and adult globins do not Knockdown of PUM1 leads to a robust increase in HBF 22 without affecting β-globin levels in human erythroid cells Moreover targeting PUM1 does not affect erythropoiesis which provides a potentially safe and effective therapeutic strategy for SCD and β-thalassemia Also it was found that elevated HbF levels in the absence of anemia in an individual with a novel heterozygous PUM1 mutation in the RNA-binding domain which suggests that PUM1 is a critical player during human hemoglobin switching
SCD is due to a single base-pair point mutation in the β-globin gene resulting in the substitution of valine for glutamic acid in the β-globin chain The pathophysiology is directly related to polymerization of deoxygenated hemoglobin leading to a cascade of pathologic events including erythrocyte sickling vaso-occlusion and hemolysis
In β-thalassemia insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells As a result a significant anemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs
The hemoglobin molecule is a tetramer composed of two subunits of α-like globin peptides and two subunits of the β-like globin peptides along with heme moieties β-globin switching from fetal γ-globin HBG1 and HBG2 to adult β-globin is a developmental process that occurs in erythrocytes at around the time of birth Fetal hemoglobin HbF induction in adult erythrocytes is an effective therapeutic strategy for SCD and β-thalassemia
Pumilio1 PUM1 is a novel target of the erythroid master transcription factor erythroid Krüppel-like factor EKLF PUM1 is a member of Pumilio-Fem3-binding factor PUF family of sequence specific RNA-binding proteins acts as a posttranscriptional repressor by binding to the 3 untranslated region 3-UTR of messenger RNA mRNA It peaks during terminal erythroid differentiation and binds to fetal γ-globin HBG1 mRNA and impairs its stability and translation HBG1 has 2 core PUM1 consensus binding sites but HBG2 and adult globins do not Knockdown of PUM1 leads to a robust increase in HBF 22 without affecting β-globin levels in human erythroid cells Moreover targeting PUM1 does not affect erythropoiesis which provides a potentially safe and effective therapeutic strategy for SCD and β-thalassemia Also it was found that elevated HbF levels in the absence of anemia in an individual with a novel heterozygous PUM1 mutation in the RNA-binding domain which suggests that PUM1 is a critical player during human hemoglobin switching
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None