Continuous Dosing of Apohemoglobin-Haptoglobin in Beta Thalassemic Mice to Establish Safety and Efficacy

Thalassemia is a blood disorder that affects the production of hemoglobin (Hb), the crucial protein responsible for carrying and delivering oxygen to tissues. It is caused by mutations in the genes that control the production of hemoglobin, leading to decreased or absent production of one of the globin chains (alpha or beta) that make up hemoglobin. Individuals with thalassemia often need regular blood transfusions to maintain adequate Hb levels. However, frequent transfusions can cause iron overload in the body, necessitating chelation therapy to remove excess iron and prevent organ damage. The iron overload also results in higher levels of hemolysis, leading to the release of free acellular Hb and heme, which the body's natural scavenging proteins (hemopexin and haptoglobin) cannot effectively handle. To address this problem, our research group has recently explored a promising solution using a bioengineered Hb and heme scavenger called apohemoglobin-haptoglobin (apoHb-Hp) complex. This complex works as a scavenger for heme and hemoglobin from the circulation, helping to eliminate vasoconstriction, enhance perfusion, and reduce inflammation. We conducted a study to test the safety and effectiveness of apoHb-Hp in beta-thalassemic mice, and the results were quite encouraging. Initially, we treated twenty beta-thalassemic mice with different dosing regimens of apoHb-Hp, ranging from 25 to 100 mg/kg. The mice received the complex every other day for a total of three doses. After the final dose, we measured various parameters, including total bilirubin concentration, plasma LDH, and plasma iron. As the dosing amount increased, there was a progressive decrease in all three measurements, reaching a therapeutic plateau at 75 mg/kg. In he second part of the study, we treated eight beta-thalassemic mice with a dose of 80 mg/kg of apoHb-Hp for six weeks, every other day. Again, we measured total bilirubin concentration, plasma LDH, and plasma iron, and observed a significant drop compared to baseline levels at the start of the study. These promising results suggest that apoHb-Hp could be a safe and effective treatment option for beta-thalassemia. Its ability to scavenge heme and Hb, along with its positive effects on various markers, makes it a potential game-changer in the management of this genetic blood disorder. Further research and testing will be necessary to fully explore the potential of apoHb-Hp as a therapeutic option for individuals with beta-thalassemi