English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

While an orphan disease in the USA, sickle cell disease (SCD), a group of genetic disorders of hemoglobin structure and function, is a major public health problem in much of the rest of the world, particularly sub-Saharan Africa. The pathophysiology of SCD stems from the formation of sickle hemoglobin polymers that deform the erythrocyte into a characteristic sickle shape, the rapidity of which is regulated by its intracellular hemoglobin concentration. Subsequent vaso-occlusion is dependent on adhesion of sickled erythrocytes, and perhaps other cellular elements, including leucocytes and platelets, to abnormal vascular endothelium using a number of receptor-ligand pairs. This propensity for vaso-occlusion may be enhanced by altered vascular tone from excessive amounts of vaso-constrictive factors or diminished amounts of vasodilatory factors. Acute pain is the hallmark symptom caused by sickle polymer formation and subsequent vaso-occlusion, and is represented in the endpoints of most previous and current clinical trial designs. Numerous failures of prior investigational agents have frustrated clinicians and patients alike. Hydroxyurea is currently the only US Food and Drug Administration-approved drug for SCD and reduces the frequency of vaso-occlusive complications in many individuals. A considerable therapeutic need remains as hydroxyurea usage is currently not approved for all types of SCD, is not always clinically effective, and requires frequent monitoring. Recent improvements in our understanding of SCD pathophysiology have generated many new therapeutic targets and associ- ated investigational agents. For example, a number of more specific fetal hemoglobin inducers and several therapies to reduce sickle polymer formation are being tested in preclinical and early phase clinical trials. Several agents that target receptor-ligand interactions which mediate cellular adhesion to vascular endothelium have shown considerable promise and are entering Phase III trials, but present some continuing challenges in clinical trial design and conduct. Gene therapy

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment