Problem

Hemolysis, the process by which the red blood cell membrane ruptures, releasing hemoglobin (Hb), is typically managed in mammalian organisms by intrinsic proteins such as hemopexin (Hpx) and haptoglobin (Hp). However, their concentrations in plasma are very limited, so, in conditions with significant hemolysis such as massive transfusion of blood, extracorporeal circuits, trauma, radiation injury, severe burns, sickle cell disease, or thalassemia, they are unable to protect against multi-organ toxicity due to the generation of reactive oxygen species, resulting in cellular and tissue damage

Solution

Researchers at OSU have developed a scalable method to remove the prosthetic group from Hb, producing apohemoglobin (apoHb), a natural Hpx-like molecule. They also created a cost-effective, large-scale purification process for Hp. Importantly, the team discovered that combining apoHb with Hp forms a novel dual scavenger protein, apoHb–Hp, that is more stable at physiological temperatures and capable of binding both Hb and heme. Upon binding, the resulting Hb–Hp complex neutralizes the toxicity of free heme and Hb and is efficiently cleared through the natural CD163-mediated macrophage uptake pathway. Beyond its detoxifying properties, the apoHb–Hp complex represents a new therapeutic platform for targeted drug delivery to CD163⁺ macrophages and monocytes, offering potential to modulate inflammation, eliminate intracellular pathogens, and treat cancers driven by pro-tumoral CD163⁺ macrophage infiltration

Applications

• Treatment of hemolytic disorders (sickle cell disease, malaria, sepsis, thalassemia, hemolytic transfusion reactions) and acute hemolysis in critical care and trauma
• Targeted delivery of anti-inflammatory or anti-cancer agents to CD163⁺ macrophages and monocytes
• Use as a carrier for imaging agents in diagnostics

Advantages

• Biocompatibility: it uses endogenous proteins, thus reducing immunogenicity
• Multi Functionality: the apoHb-Hp complex integrates heme and Hb detoxification with potential for targeted therapeutic delivery, enhancing its clinical utility
• Precision Targeting: the technology leverages the body’s natural clearance mechanisms for precision targeting
• Therapeutic flexibility: this adaptable platform is suitable for a wide range of drugs and disease indications
• Improved stability: the complex has been engineered to resist degradation and maintain activity for in vivo applications

Seeking opportunities for out-licensing or collaboration