ATP-adenosine-GSH crosslinked Hb, an oxygen carrier with pharmacological properties for multiple therapeutic indications

Abstract

The quest to develop a viable substitute for human blood has been ongoing for many decades. Many attempts to create an effective blood substitute fall short because of toxicity issues and at present no product is commercially available. Armed with an awareness of the problems associated with the performance of the first generation blood substitute products, which are linked to hemoglobin's (Hb) intrinsic toxicity that causes hypertension, oxidative and inflammatory reactions, gastrointestinal disorders and even heart attack and stroke, researchers at Texas Tech University Health Sciences Center created a novel concept of pharmacological cross-linking of Hb with ATP, adenosine and reduced glutathione (GSH) that resulted in the non-toxic and effective ATP-ADO-GSH-Hb product. This novel blood substitute possesses vasodilatory, anti-oxidant, anti-inflammatory and erythropoietic properties; all of which are beneficial to the patients suffering from acute and chronic anemias, sickle cell disease, ischemic diseases including heart attack and stroke, and cancer. ATP-ADO-GSH-Hb and its manufacturing technology have been extensively tested including viral and prion clearance validation studies and various non-clinical pharmacology, toxicology, genotoxicity and efficacy tests. The effects of ATP-ADO-GSH-Hb on appropriate physiological measures in human cell systems, normal animals and disease models have also been determined. The clinical proof-of-concept was carried out in sickle cell anemia patients. The obtained results confirmed that pharmacologic cross-linking of Hb molecules with ATP, adenosine and GSH is highly effective in designing a viable blood substitute for a wide array of therapeutic uses.