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Human Genomics Jun 2021For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms... (Review)
Review
For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms of effectiveness and safety. So far, the most prevalent and promising treatment options for patients with β-types hemoglobinopathies, among others, predominantly include drug treatment and gene therapy. Despite the significant improvements of such interventions to the patient's quality of life, a variable response has been demonstrated among different groups of patients and populations. This is essentially due to the complexity of the disease and other genetic factors. In recent years, a more in-depth understanding of the molecular basis of the β-type hemoglobinopathies has led to significant upgrades to the current technologies, as well as the addition of new ones attempting to elucidate these barriers. Therefore, the purpose of this article is to shed light on pharmacogenomics, gene addition, and genome editing technologies, and consequently, their potential use as direct and indirect genome-based interventions, in different strategies, referring to drug and gene therapy. Furthermore, all the latest progress, updates, and scientific achievements for patients with β-type hemoglobinopathies will be described in detail.
Topics: Anemia, Sickle Cell; Gene Editing; Genetic Therapy; Hemoglobinopathies; Humans; beta-Globins; beta-Thalassemia
PubMed: 34090531
DOI: 10.1186/s40246-021-00329-0 -
Pediatric Annals Feb 2024Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy that affects individuals worldwide. The mutation in the beta-globin gene leads to abnormal... (Review)
Review
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy that affects individuals worldwide. The mutation in the beta-globin gene leads to abnormal hemoglobin production, sickle hemoglobin, which polymerizes under stress leading to, among other end-organ manifestations, chronic hemolytic anemia, debilitating vaso-occlusive crises, and stroke. Unfortunately, chronic stress on end-organs impacts the life expectancy of patients with SCD, which in the United States averages 43 years, approximately 36 years less than people without the disease. Here, we review the progress made in curative interventions for those with SCD, namely allogeneic hematopoietic cell transplantation and gene therapy. These interventions continue to evolve as we better understand SCD pathophysiology, use new graft-versus-host disease prophylaxis regimens, expand stem cell donor options, and understand the genetic control of hemoglobin production. Although significant progress has been made, many gaps remain in the successful implementation of these interventions globally and for all patients. .
Topics: Humans; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Stroke
PubMed: 38302122
DOI: 10.3928/19382359-20231205-06 -
Blood Sep 2022
Topics: Anemia, Sickle Cell; Child; Hemoglobinopathies; Humans; Ticagrelor
PubMed: 36173660
DOI: 10.1182/blood.2022017213 -
Acta Bio-medica : Atenei Parmensis Sep 2021Starting from 2021, Acta Biomedica Parmensis will dedicate an annual update to the "Advances in Hemoglobinopathies". The section editor of this new editorial initiative...
Starting from 2021, Acta Biomedica Parmensis will dedicate an annual update to the "Advances in Hemoglobinopathies". The section editor of this new editorial initiative is prof. Ashraf T Soliman, Pediatrician and Endocrinologist at Hamad Medical Center (HMC) of Doha. Prof Soliman is a pionier in the study of endocrine complications in hemoglobinopathies and effects of blood transfusions on spermatogenesis. He collaborates strictly with prof. Mohamed Yassin, Hematologist-Oncologist at MCH and the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). This issue of Acta Biomedica contains three articles on: The different patterns of insulin response during Oral Glucose Tolerance Test (OGTT) in transfused young patients with β- Thalassemia; Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey and The effects of treatment with blood transfusion, iron chelation and hydroxyurea on puberty, growth and spermatogenesis in sickle cell disease,.
Topics: Anemia, Sickle Cell; Emigration and Immigration; Hemoglobinopathies; Humans; Male; Thalassemia; beta-Thalassemia
PubMed: 34487058
DOI: 10.23750/abm.v92i4.11927 -
Med (New York, N.Y.) Feb 2021Studies of the major hemoglobin disorders, β-thalassemia and sickle cell disease (SCD), have laid a foundation for molecular medicine. While enormous progress has been... (Review)
Review
Studies of the major hemoglobin disorders, β-thalassemia and sickle cell disease (SCD), have laid a foundation for molecular medicine. While enormous progress has been made in understanding gene structure and regulation, translating molecular insights to therapy for the many individuals affected with these disorders has been challenging. Advances in three activities have recently converged to bring novel genetic and potentially curative treatments to clinical trials. First, improved lentiviral vectors for gene transfer into hematopoietic stem cells have revived somatic gene therapy for blood disorders. Second, elucidation of regulatory factors and mechanisms that control the normal developmental switch from fetal to adult hemoglobin has provided a route to reactivation of the fetal form for therapy. Third, revolutionary methods of gene engineering permit molecular insights to be leveraged for patients. Here I review how the promise of molecular medicine to bring transformative treatments to the clinical arena is finally being realized.
Topics: Adult; Genetic Therapy; Hemoglobinopathies; Hemoglobins; Humans; Molecular Medicine; beta-Thalassemia
PubMed: 33688634
DOI: 10.1016/j.medj.2020.12.011 -
Clinical Chemistry Sep 2021
Topics: Chromatography, High Pressure Liquid; Fetal Hemoglobin; Hemoglobinopathies; Hemoglobins, Abnormal; Humans
PubMed: 34470038
DOI: 10.1093/clinchem/hvab049 -
The Lancet. Global Health Jan 2022
Topics: Developing Countries; Hemoglobin, Sickle; Hemoglobinopathies; Humans; Infant, Newborn; Neonatal Screening
PubMed: 34919844
DOI: 10.1016/S2214-109X(21)00559-3 -
Current Opinion in Hematology May 2020In this work we briefly summarize the key features and currently available conventional therapies for the two main β-hemoglobinopathies, sickle cell disease (SCD) and... (Review)
Review
PURPOSE OF REVIEW
In this work we briefly summarize the key features and currently available conventional therapies for the two main β-hemoglobinopathies, sickle cell disease (SCD) and β-thalassemia, and review the rapidly evolving field of novel and emerging genetic therapies to cure the disease.
RECENT FINDINGS
Gene therapy using viral vectors or designer nuclease-based gene editing is a relatively new field of medicine that uses the patient's own genetically modified cells to treat his or her own disease. Multiple different approaches are currently in development, and some have entered phase I clinical studies, including innovative therapies aiming at induction of fetal hemoglobin.
SUMMARY
Early short-term therapeutic benefit has been reported for some of the ongoing clinical trials, but confirmation of long-term safety and efficacy remains to be shown. Future therapies aiming at the targeted correction of specific disease-causing DNA mutations are emerging and will likely enter clinical testing in the near future.
Topics: Anemia, Sickle Cell; Genetic Therapy; Genetic Vectors; Humans; beta-Thalassemia
PubMed: 32205585
DOI: 10.1097/MOH.0000000000000581 -
Clinical Biochemistry Aug 2023Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000...
BACKGROUND
Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification.
CASE REPORT
Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving.
CONCLUSION
Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.
Topics: Male; Humans; Hemoglobins, Abnormal; Hemoglobinopathies; Thalassemia; Hemoglobin A2; Electrophoresis, Capillary
PubMed: 37236295
DOI: 10.1016/j.clinbiochem.2023.110589 -
Der Ophthalmologe : Zeitschrift Der... Oct 2021Sickle cell disease (SCD) is a hereditary hemoglobinopathy, which leads to microcirculatory disturbances of various organ systems through recurrent vaso-occlusive... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is a hereditary hemoglobinopathy, which leads to microcirculatory disturbances of various organ systems through recurrent vaso-occlusive episodes, with a possibly fatal outcome. Sickle cell retinopathy (SCR) is the best described ocular manifestation of SCD. Irrespective of the presence of peripheral SCR, sickle cell maculopathy (SCM) can occur early in the course of the disease.
METHODS
Review of the international and German literature on ocular involvement in SCD with a focus on SCR and SCM and an overview of current systemic therapeutic approaches in SCD on the occasion of the presentation of two patients with HbSS SCD.
RESULTS AND CONCLUSION
In contrast to SCR, SCM with temporal thinning of the inner retinal layers has only been increasingly described in the literature in the last 5 years, with the advent of SD-OCT and OCTA. Irrespective of the presence of SCR, as many as about half of the patients may develop SCM early in the course of the disease. As a result of progress in systemic therapeutic options and due to migration, the clinical picture will occur more often also in Germany. By knowing about this complication of SCD an early diagnosis can be made and unnecessary diagnostics can be avoided.
Topics: Anemia, Sickle Cell; Humans; Macular Degeneration; Microcirculation; Retina; Retinal Diseases
PubMed: 33502544
DOI: 10.1007/s00347-020-01319-8