Gene therapy and editing in the treatment of hereditary blood disorders: Medical and ethical aspects

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be useful to evaluate the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used.

Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders

In red blood cell (RBC) diseases, the spleen contributes to anemia by clearing the damaged RBCs, but its unique ability to mechanically challenge RBCs also poses the risk of inducing other pathogenic effects. We have analyzed RBCs in hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), two typical examples of blood disorders that result in membrane protein defects in RBCs. We use a two-component protein-scale RBC model to simulate the traversal of the interendothelial slit (IES) in the human spleen, a stringent biomechanical challenge on healthy and diseased RBCs that cannot be directly observed in vivo. In HS, our results confirm that the RBC loses surface due to weakened cohesion between the lipid bilayer and the cytoskeleton and reveal that surface loss may result from vesiculation of the RBC as it crosses IES. In HE, traversing IES induces sustained elongation of the RBC with impaired elasticity and fragmentation in severe disease. Our simulations thus suggest that in inherited RBC disorders, the spleen not only filters out pathological RBCs but also directly contributes to RBC alterations. These results provide a mechanistic rationale for different clinical outcomes documented following splenectomy in HS patients with spectrin-deficient and ankyrin-deficient RBCs and offer insights into the pathogenic role of human spleen in RBC diseases.

Should Premarital Screening for Blood Disorders be an Obligatory Measure in Oman?

Due to the high rate of consanguineous marriages in Oman, there is a correspondingly high prevalence of hereditary blood disorders, particularly sickle cell disease and β-thalassaemia. This article proposes the possibility of implementing mandatory premarital carrier screening for blood disorders in Oman, while giving due consideration to potential social and cultural obstacles. Although the implementation of such legislation would require collaboration between different sectors and may negatively affect the autonomy of certain individuals, mandatory premarital screening would help to alleviate the burden of hereditary blood disorders on the national healthcare system, as well as reduce avoidable suffering among carriers and their families.

Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease

The biconcave shape and corresponding deformability of the human red blood cell (RBC) is an essential feature of its biological function. This feature of RBCs can be critically affected by genetic or acquired pathological conditions. In this review, we highlight new dynamicin vitroassays that explore various hereditary blood disorders and parasitic infectious diseases that cause disruption of RBC morphology and mechanics. In particular, recent advances in high-throughput microfluidic devices make it possible to sort/identify healthy and pathological human RBCs with different mechanobiological characteristics.

A community-based study of common hereditary blood disorders in Oman

Weassessed the prevalence of three common hereditary blood disorders [sickle-cell and beta-thalassaemia traits and glucose 6-phosphate dehydrogenase deficiency] among the Omani population. We interviewed a representative sample of 6103 Omani households and blood samples from 6342 children aged 0-5 years were collected. About 27% of Omani males had inherited glucose-6-phosphate dehydrogenase deficiency [compared with 11% of females] while countrywide prevalence rates for the sickle-cell and beta-thalassaemia traits were estimated to be 5.8% and 2.2% respectively and showed no significant gender differences. There was a significant association between all three disorders and region of the country.