&lt;p&gt;Nucleic Acid Therapy for β-Thalassemia&lt;/p&gt;

d'Arqom, Annette

doi:10.2147/btt.s265767

Cited by 6 publications

(6 citation statements)

References 91 publications

(81 reference statements)

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“…New approaches that can rapidly and selectively remove excess iron from the most affected organs would save many patients from an untimely departure. This is in combination with new generation approaches such as gene therapy, gene knockout, or silencing which could lead to better treatment for iron overload diseases. − We believe that the recent approval of Bluebird Bio’s gene therapy approach (ZYNTEGLOR) for transfusion-dependent β-thalassaemia further drives the field in this direction …”

Section: Discussionmentioning

confidence: 99%

Role of Iron in the Molecular Pathogenesis of Diseases and Therapeutic Opportunities

et al. 2021

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Iron is an essential mineral that serves as a prosthetic group for a variety of proteins involved in vital cellular processes. The iron economy within humans is highly conserved in that there is no proper iron excretion pathway. Therefore, iron homeostasis is highly evolved to coordinate iron acquisition, storage, transport, and recycling efficiently. A disturbance in this state can result in excess iron burden in which an ensuing iron-mediated generation of reactive oxygen species imparts widespread oxidative damage to proteins, lipids, and DNA. On the contrary, problems in iron deficiency either due to genetic or nutritional causes can lead to a number of iron deficiency disorders. Iron chelation strategies have been in the works since the early 1900s, and they still remain the most viable therapeutic approach to mitigate the toxic side effects of excess iron. Intense investigations on improving the efficacy of chelation strategies while being well tolerated and accepted by patients have been a particular focus for many researchers over the past 30 years. Moreover, recent advances in our understanding on the role of iron in the pathogenesis of different diseases (both in iron overload and iron deficiency conditions) motivate the need to develop new therapeutics. We summarized recent investigations into the role of iron in health and disease conditions, iron chelation, and iron delivery strategies. Information regarding small molecule as well as macromolecular approaches and how they are employed within different disease pathogenesis such as primary and secondary iron overload diseases, cancer, diabetes, neurodegenerative diseases, infections, and in iron deficiency is provided.

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Section: Discussionmentioning

confidence: 99%

Role of Iron in the Molecular Pathogenesis of Diseases and Therapeutic Opportunities

et al. 2021

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“…Therefore, transfusion remains the recommended treatment option in Indonesia. 2 The Thalassemia International Federation classifies thalassemia by transfusion need into transfusion-independent thalassemia and transfusiondependent thalassemia. 3 Repeated transfusions can cause various complications.…”

Section: Introductionmentioning

confidence: 99%

Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody

Tambunan

Ugrasena

Aryati

2023

IJGM

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Introduction: Antibody formation in transfusion-dependent thalassemia is associated with chronic hemolysis and repeated transfusions. Hemolysis produces heme, which mediates B-cell differentiation into plasma cells and produces antibodies influenced by interleukin-21 .Objective: This study aimed to compare IL-21 levels, plasma cell percentage, and red blood cell antibodies between positive and negative allo-autoantibody thalassemia before and after hemin administration. Materials and Methods: This research employed a quasi-experimental nonequivalent control group pre-test and post-test design performed from April to November 2021 at Soetomo Academic Hospital in Surabaya, Indonesia. Heparinized blood samples of 5 mL and 4 mL and EDTA blood samples of 3 mL were taken from positive (29 patients) and negative (28 patients) allo-autoantibody thalassemia participants. Hemin 20 µM was added to 5 mL of heparinized blood, incubated for 2 hours, prepared into peripheral blood mononuclear cells (PBMCs), and cultured for 3 days. The percentage of plasma cells (CD38+CD184+) of cultured and uncultured PBMCs was measured by BD FACSCalibur Flow Cytometer. IL-21 levels of plasma and supernatants were measured with Sandwich Enzyme-Linked Immunosorbent Assay by Elabscience. Red blood cell antibodies were detected by QWALYS 3 E.M. Technology. Autoantibodies were determined by the Grifols gel tube method. Results: IL-21 levels were significantly different in the positive and negative allo-autoantibody thalassemia groups after hemin administration. The percentage of plasma cells in the positive allo-autoantibody group increased significantly after the administration of hemin. The percentage of plasma cells between thalassemia groups was not significantly different before the hemin administration but increased significantly after it. Red blood cell antibodies after the administration of hemin were significantly different in the negative allo-autoantibody group but not significantly different in the positive allo-autoantibody group. Conclusion: Hemin administration affected IL-21 levels, plasma cell percentage, and antibody formation in positive and negative allo-auto antibody thalassemia.

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“…However, several limitations challenge their implementation, such as stability, delivery method, suitable vector, and optimal nucleic acid dose. 2 …”

Section: Introductionmentioning

confidence: 99%

Role of Hemin in the Immune Response of T Follicular Helper Lymphocytes Expressing T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Domains, Programmed Cell Death-1, and Interleukin-21 in Allo-Auto Positive and Negative Thalassemia

Tambunan¹,

Ugrasena²,

Aryati³

2023

JBM

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Introduction Repeated transfusions in thalassemia patients can cause several complications, including alloimmunization and autoimmunization. Purpose This study compares the immune response of T follicular helper (Tfh) lymphocytes expressing T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), programmed cell death-1 (PD-1), and interleukin-21 (IL-21) between patients with allo-auto positive and negative thalassemia before and after hemin administration. Materials and Methods This study used a quasi-experimental pre- and post-test design and was performed between April and November 2021 at the Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. It enrolled 29 patients with allo-auto positive thalassemia and 28 with allo-auto negative, and 9 mL of whole blood (WB) was drawn from each patient. Hemin solution (20 µM) was added to 5 mL of WB, incubated for two hours, processed into peripheral blood mononuclear cells (PBMCs) in RPMI media, and cultured with 5% CO 2 for three days. The 4 mL WB sample was also processed into PBMCs. PBMC cells cultured and without cultured were examined by flow cytometry using a BD FACSCalibur after surface and intracellular staining. Differences in Tfh cells expressing TIGIT, PD-1, and IL-21 between thalassemia groups before and after hemin administration were compared using independent t -tests or Mann–Whitney U -tests (p < 0.05). Results Tfh cell expression did not differ between groups before hemin administration and increased after hemin administration. The increase in Tfh cell expression was higher in the allo-auto positive group. TIGIT and PD-1 expression in Tfh cells did not differ between groups, but TIGIT decreased after hemin administration in contrast to PD-1 result. IL-21 expression in Tfh cells did not differ between groups and did not change after hemin administration. Conclusion Hemin affected the expression of Tfh cells in both group thalassemia, but there was no difference of Tfh cell expression between the groups.

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<p>Nucleic Acid Therapy for β-Thalassemia</p>

Cited by 6 publications

References 91 publications

Role of Iron in the Molecular Pathogenesis of Diseases and Therapeutic Opportunities

Role of Iron in the Molecular Pathogenesis of Diseases and Therapeutic Opportunities

Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody

Role of Hemin in the Immune Response of T Follicular Helper Lymphocytes Expressing T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Domains, Programmed Cell Death-1, and Interleukin-21 in Allo-Auto Positive and Negative Thalassemia

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