Addition of Multimodal Therapy to Standard Management of Steady State Sickle Cell Disease

Abstract

Most people on folic acid to boost erythropoiesis and prophylactic antimicrobials, the standard management of steady state sickle cell disease (SCD), have unacceptable numbers of crises. The objective of this study was to evaluate the effects of adding multimodal therapy with potassium thiocyanate and omega-3 fatty acids to the standard management of steady state SCD. Pre- and post-treatment numbers of crises and other disease indices were compared in 16 HbSS individuals on folic acid and paludrine after 12 months of adding eicosapentaenoic acid 15 mg/kg/day, docosahexaenoic acid 10 mg/kg/day, and potassium thiocyanate 1-2 mL/day, each milliliter of which contained 250 mg of thiocyanate and 100 micrograms of iodine to prevent hypothyroidism: a possible side-effect due to competitive inhibition of the transport of iodide into the thyroid gland by thiocyanate. Median number of crises reduced from 3/yr to 1/yr (P < 0.0001). There was no evidence of impaired thyroid function. Plasma level of tri-iodothyronine improved (P < 0.0001). Steady state full blood count and bilirubin level did not change significantly. The findings suggest that addition of potassium thiocyanate and eicosapentaenoic and docosahexaenoic acids to standard management of steady state SCD reduces the number of crises. This observation needs to be evaluated in larger studies.

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

“…These findings indicated the important role of fatty acid abnormality in the chronic inflammatory state associated with the disease [14,15]. In addition, our group and others have shown that supplementing SCD patients with omega-3 fatty acids corrects cell membrane abnormalities and confer protection against vaso-occlusive pain episodes, severe anaemia and oxidative stress [16][17][18][19], and improves red blood cells flexibility in mice [20]. However, little is known about the potential antiinflammatory role of n−3 fatty acids in SCD.…”

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial)

“…1,12,13 Given the complex nature of SCD pathophysiology, a multimodal therapy or a single drug with multiple mechanisms of action may be necessary to achieve clinical effectiveness. 14,15 The multiple biological and pleiotropic effects of the v-3 fatty acid docosahexaenoic acid (DHA, 22:6v3) that include, but are not limited to, its antioxidant, anti-inflammatory, antiadhesion, anti-aggregation properties and its positive effects on erythrocyte rheology and vasodilatation [16][17][18][19][20][21][22][23][24][25] all offer potential therapeutic benefits in SCD. In addition, resolvins, endogenous lipid mediators generated from DHA and eicosapentaenoic acid (EPA; 20:5v3), have been shown to increase nitric oxide availability and reduce inflammatory pain.…”

“…20,[27][28][29] Treatment of patients with SCD with the v-3 fatty acids DHA and EPA has been shown to correct cell membrane fatty acid balance and confer protection against vaso-occlusive pain episodes, hemolysis, oxidative stress, and inflammation. [16][17][18][19][20][21] Treatment of mouse models of SCD with DHA and EPA also improves erythrocyte flexibility and reduces vascular endothelial activation and sickle cell-related end-organ injury. 30,31 SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology, or ALT) that enhances DHA bioavailability and overcomes the variable absorption related to dietary fat ("food effect") 32,33 To investigate the safety and efficacy of 3 dose levels of SC411 in children with SCD, the phase 2 SCOT (Sickle Cell Omega-3 Treatment) trial (NCT02973360) was conducted at 11 sites in the United States.…”