Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Hwy Shreveport, LA, USA.
Sancilio & Company, Inc, Stuart, FL, USA; Center of Molecular Biology and Biotechnology (CMBB), Florida Atlantic University, USA.
Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102110. doi: 10.1016/j.plefa.2020.102110. Epub 2020 May 3.
Sickle cell disease (SCD) is one of the most common inherited blood disorder among African Americans affecting 70,000-100,000 individuals in the United States. It is characterized by abnormal hemoglobin (HbS) which develops into severe hemolytic anemia and vaso-occlusive crisis. Therefore, patients with SCD suffer from a chronic state of inflammation, which is responsible for multiple organ damage, ischemic attacks, and premature death. Another major hallmark of SCD patients is the abnormally low levels of omega-3 fatty acids, especially docosahexaenoic acid (DHA) in their red blood cell membranes. Treatment with DHA can reduce red blood cell adhesion and enhance cerebral blood flow, thus, our main goal is to investigate the effect of SC411, which is a novel, highly purified DHA ethyl ester formulation with a proprietary delivery platform in SCD. Utilizing a transgenic mouse model of SCD (HbSS-Townes) and recurrent hypoxic challenges (10%O, 0.5% CO and balance N for 3 h) to mimic ischemic-like conditions, our data suggest that SC411 can elevate blood DHA and eicosapentaenoic acid (EPA) levels after 8 weeks of treatment. SC411 can also decrease arachidonic acid (AA) and sickling of red blood cells. In addition, SC411-treated SCD mice showed presented with cerebral blood flow, alleviated neuroinflammation, and revived working memory which ultimately enhanced overall survival. In summary, this study suggests that treatment with SC411 improves cellular and functional outcomes in SCD mice. This finding may provide novel therapeutic opportunities in the treatment against ischemic injury elicited by SCD.
镰状细胞病（SCD）是美国最常见的遗传性血液病之一，影响 7 万至 10 万人。其特征是异常血红蛋白（HbS），发展为严重溶血性贫血和血管阻塞性危象。因此，SCD 患者患有慢性炎症状态，这是导致多器官损伤、缺血发作和过早死亡的原因。SCD 患者的另一个主要特征是其红细胞膜中异常低水平的ω-3 脂肪酸，特别是二十二碳六烯酸（DHA）。DHA 治疗可以减少红细胞黏附并增强脑血流，因此，我们的主要目标是研究新型、高度纯化的 DHA 乙酯制剂 SC411 在 SCD 中的作用。利用 SCD 的转基因小鼠模型（HbSS-Townes）和反复缺氧挑战（10%O、0.5%CO 和平衡 N 3 小时）模拟类似缺血的条件，我们的数据表明，SC411 可以在 8 周治疗后提高血液 DHA 和二十碳五烯酸（EPA）水平。SC411 还可以减少花生四烯酸（AA）和红细胞镰状化。此外，SC411 治疗的 SCD 小鼠表现出脑血流增加、神经炎症减轻和工作记忆恢复，最终提高整体存活率。总之，这项研究表明，SC411 治疗可改善 SCD 小鼠的细胞和功能结果。这一发现可能为治疗 SCD 引起的缺血损伤提供新的治疗机会。
