Abstract
Sickle cell disease (SCD) is a genetic disorder predominantly affecting individuals of African descent, with a significant global health burden. SCD is characterized by intravascular hemolysis, driven by the polymerization of mutated hemoglobin within red blood cells (RBCs), leading to vascular inflammation, organ damage, and heme toxicity. Clinical manifestations include acute pain crises, hemolytic anemia, and multi-organ dysfunction, imposing substantial morbidity and mortality challenges. Current therapeutic strategies mitigate these complications by increasing the concentration of RBCs with normal hemoglobin via transfusion, inducing fetal hemoglobin, restoring nitric oxide signaling, inhibiting platelet-endothelium interaction, and stabilizing hemoglobin in its oxygenated state. While hydroxyurea and gene therapies show promise, each faces distinct challenges. Hydroxyurea’s efficacy varies among patients, and gene therapies, though effective, are limited by issues of accessibility and affordability. An emerging frontier in SCD management involves harnessing endogenous clearance mechanisms for hemolysis products. A recent work by Heggland et al. showed that CD-36-like proteins mediate heme absorption in hematophagous ectoparasite, a type of parasite that feeds on the blood of its host. This discovery underscores the need for further investigation into scavenger receptors (e.g., CD36, SR-BI, SR-BII) for their possible role in heme uptake and detoxification in mammalian species. In this review, we discussed current SCD therapeutics and the specific stages of pathophysiology they target. We identified the limitations of existing treatments and explored potential future developments for novel SCD therapies. Novel therapeutic targets, including heme scavenging pathways, hold the potential for improving outcomes and reducing the global burden of SCD.
Document Type
Article
Publication Date
9-2024
Digital Object Identifier (DOI)
https://doi.org/10.3389/fphys.2024.1474569
Funding Information
The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by Grants NIH R35GM141478, VA 1I01BX004639 and VA I01BX006408 (to X-AL). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or VA.
Repository Citation
Xue, Jianyao and Li, Xiang-An, "Therapeutics for sickle cell disease intravascular hemolysis" (2024). Markey Cancer Center Faculty Publications. 263.
https://uknowledge.uky.edu/markey_facpub/263
Notes/Citation Information
© 2024 Xue and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.