Recombinant DNA Technology and Gene Therapy Using Viruses
Patricia G. Melloy in Viruses and Society, 2023
Although a small number of gene therapy products have been approved in the United States, many are being tested right now, including potential treatment for monogenic disorders that have been studied for many years. As mentioned earlier, both cystic fibrosis (CF) and sickle cell disease (SCD) are well-known monogenic disorders. Cystic fibrosis involves a defective chloride ion transporter causing mucus buildup in the lungs, making patients prone to infections, among other issues. Other organs, such as parts of the digestive system, are also affected in CF. Physicians and scientists have been working on gene therapy approaches to treat CF for many years. So far, there are no approved gene therapy treatments, although several approaches are being tested in clinical trials. Since CF can affect more than one organ, determining where to deliver the therapy is one challenge, in addition to providing a treatment that is long lasting (Foundation 2022; Colavito 2007). Sickle cell disease (also known as sickle cell anemia) involves the loss of functional adult hemoglobin for oxygen transport in the blood due to a defective beta-globin gene. Clinical trials in SCD patients are underway to use a lentivirus-based vector to restore a normal copy of the beta-globin gene. A second treatment approach for SCD involves using gene therapy to reactivate expression of the gamma-globin gene, a component of fetal hemoglobin, to substitute for the defective beta-globin in the adult hemoglobin form (Eisenstein 2021; Kunz and Kulozik 2020).
Sickle Cell Disease
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
Sickle cell disease describes a group of inherited disorders characterized by the presence of HbS. Sickle cell disease is associated with a mild to moderate chronic anemia. The term sickle cell disease includes sickle cell anemia (HbSS) (70% of cases), hemoglobin S combined with hemoglobin C (HbSC) (most of the remaining cases), hemoglobin S combined with β-thalassemia (HbSβ+ or HbSβ0), and other double heterozygous conditions causing sickling and thus, clinical disease (e.g., hereditary persistence of fetal hemoglobin (HgS/HPHP), and hemoglobin E (HbS/HbE) [7]. The clinical manifestations vary among these genotypes, with HbSβ0 usually with a similar severe phenotype as HbSS, HbSC associated with intermediate disease, and HbSβ+, HbSHPHP, and HbSE with mild or symptom-free disease [1, 5]. The term sickle cell anemia includes HbSS, and also HbSβ0 (due to its similar phenotype). The sickle cell trait is the heterozygous inheritance of HgbS and is characterized by benign clinical course without anemia, with protection against malaria [8].
Carrier Screening For Inherited Genetic Conditions
Vincenzo Berghella in Obstetric Evidence Based Guidelines, 2022
Sickle cell disease refers to a group of autosomal recessive disorders involving hemoglobin S. Hemoglobin S differs from hemoglobin A due to a single nucleotide substitution in the beta-globin gene on chromosome 11. The most severe form of sickle cell disease, sickle cell anemia, occurs in individuals with two copies of hemoglobin S. Sickle cell disorders can also occur in individuals who have hemoglobin S and another abnormality of B-globin structure or production such as hemoglobin C or beta-thalassemia. Sickle cell disease occurs most commonly in people of African origin. One in 12 African Americans has sickle cell trait. Patients with sickle cell disease are prone to distortion, or sickling, of their red blood cells under conditions of decreased oxygen tension. These distorted cells can result in increased viscosity, hemolysis, and anemia, resulting in interrupted blood supply to vital organs. These vasoocclusive crises can cause interruption of normal perfusion and function of several organs, including the spleen, lungs, kidney, heart, and brain. See Chap. 15 in Maternal-Fetal Medicine Evidence Based Guidelines.
Attitudes and practices of unmarried adults towards sickle cell disease: emergent factors from a cross sectional study in Nigeria’s capital
Published in Hematology, 2022
Obi Peter Adigwe, Godspower Onavbavba, Solomon Oloche Onoja
Globally, the prevalence of the disease is highest in sub-Saharan Africa, with Nigeria saddled with the highest burden of carrier prevalence ranging from 25% to 30% [5,6]. Furthermore, in the country, sickle cell anaemia occurs in approximately 3% of all births [7–9]. Some of the common characteristics of sickle cell disease include chronic haemolytic anaemia and recurrent vaso-occlusion, with the latter being responsible for painful crises associated with the disease. Another common feature of the condition is chronic vasculopathy triggered by free heme resulting in nitric oxide scavenging and upregulation of adhesion molecules in reticulocytes neutrophils and endothelial cells [10,11]. One of the major causes of mortality among children is overwhelming bacterial infections occurring due to encapsulated organisms, particularly pneumococcus [1213]. Other common causes of death include splenic sequestration [14], acute chest syndrome [15], stroke [16,17] and multiple organ failure [18]. There is therefore substantial evidence that the disease constitutes a high mortality risk for under-five sickle cell disease patients who live in areas without adequate access to healthcare [19]. This is further complicated by the fact that empirical evidence now correlates malaria episodes with increased risk of crises, alongside the possible morbidity and mortality associated with these events [20,21].
Role of Oxidative Stress and the Protective Effect of Fermented Papaya Preparation in Sickle Cell Disease
Published in Hemoglobin, 2022
Prashant P. Warang, Nikhil S. Shinde, Vinod D. Umare, Prajyot V. Deshmukh, Kanjaksha Ghosh, Manisha R. Madkaikar, Roshan B. Colah, Malay B. Mukherjee
Sickle cell disease is hereditary hemolytic anemia due to a mutation in the β-globin gene that encodes for an abortive globin and hemoglobin (Hb). Sickle cell disease, like other hemoglobinopathies, was reported to be associated with oxidative stress. Oxidative stress is the result of imbalance between the enhanced generation of reactive oxygen species (ROS) and low levels of antioxidants, which triggers a series of oxidative reactions damaging lipids, proteins, and DNA ultimately leading to hemolysis of red blood cells (RBCs). Oxidative stress in sickle cell disease patients leads to multiple pathophysiologic mechanisms, such as hemolysis, endothelial damage, reduced nitric oxide (NO) bioavailability, and vaso-occlusion leading to chronic organ damage [1]. Fermented papaya preparation (FPP) is a health product with anti-oxidative properties, resulting from yeast fermentation of carica papaya. It has previously been shown that FPP is efficient in limiting oxidative stress in β-thalassemia (β-thal), Hb E (HBB: c.79G > A)/β-thal, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria [2]. To the best of our knowledge, anti-oxidative effects of FPP in sickle cell disease patients have not yet been studied.
Preconception care counselling among women with sickle cell anaemia in the south of Iran: a qualitative study based on social marketing model
Published in Journal of Obstetrics and Gynaecology, 2022
Asiyeh Pormehr-Yabandeh, Teamur Aghamolaei, Zahra Hosseini, Nasibeh Roozbeh, Amin Ghanbarnezhad
Sickle cell anaemia is a common inherited blood cell disorder worldwide (Nasiri et al. 2020). This disease is seen annually among 300,000 neonates in the world (Ghafuri et al. 2017). The incidence rate of sickle cell heterozygote and sickle cell anaemia in the south of Iran is about 1.43 and 0.1, respectively. The incidence rate of sickle cell disease in the centre of Iran is 8%. This rate is 6.1 in Kermanshah (Sar-Pol-Zahab) (Saeidi et al. 2014). The preconception period is of great significance among sickle cell patients. The prevalence of the disease in the preconception period in recent investigations is due to the increasing number of women afflicted with preconception sickle cell which, in turn, results from more medical care provision (Omole-Ohonsi et al. 2012). As a work of research in preconception care providing clinics in Nigeria showed, the incidence rate of sickle cell disease is 19.77. The incidence rate of the sickle cell was also reported in 0.14% of pregnancies. Thus, the rate of the sickle cell disease has been reported to be high in this geographic region (Nwabuko et al. 2016). Many investigations indicated the adverse effects of pregnancy on women with sickle cell disease. These women had higher chances of preconception consequences and infections (Desai et al. 2017).
Related Knowledge Centers
- Anemia
- Chronic Pain
- Dactylitis
- Heredity
- Stroke
- Hematologic Disease
- Hemoglobin
- Red Blood Cell
- Pathogenic Bacteria
- Hemoglobin Subunit Beta