July 31, 2007 Studies in mice suggest that a red blood cell substitute based on human hemoglobin could be a promising new treatment for sickle cell disease in humans.
The August issue of the journal Anesthesiology features a study showing that a newly developed "hemoglobin-based oxygen carrier" (HBOC) called HRC 101 (Hemosol, Mississauga, Ontario, Canada) dramatically improves survival in mice with "sickled" red blood cells exposed to low-oxygen conditions. "HRC 101 warrants further evaluation as a therapeutic modality in sickle cell disease," concludes the study, led by Dr. Mark W. Crawford of The Hospital for Sick Children, University of Toronto.
Dr. Crawford and colleagues report on experiments in mice genetically engineered to produce a condition similar to human sickle cell disease—an inherited disorder in which the red blood cells have an abnormal sickled or crescent-moon shape. Especially during attacks called "sickle cell crises," the sickle cells obstruct small blood vessels, blocking blood flow to organs and other parts of the body and thereby depriving the body’s tissues of oxygen.
The researchers compared the effects of low oxygen conditions—intended to mimic sickle cell crisis—in sickle-cell versus normal mice (all animals were under anesthesia [asleep] during the procedure). Some mice received HRC 101 to see if the red cell substitute could protect organs against the damaging effects of obstructed blood flow, while others, in control groups, received a placebo.
All of the normal mice tolerated a one-hour period of low oxygen. By comparison, untreated sickle-cell mice did not tolerate the low-oxygen condition.
In contrast, more sickle-cell mice that received the artificial oxygen carrier tolerated the one-hour period of decreased oxygen. HRC 101 allowed the sickle-cell mice to tolerate the low-oxygen environment about five times longer.
Patients with sickle cell disease need frequent blood transfusions to treat anemia and other complications. Although transfusions are beneficial, they have several short- and long-term risks.
"Hemoglobin-based oxygen carriers are red cell substitutes that can be used to increase oxygen-carrying capacity and intravascular volume," according to the authors. HRC 101 may be useful in the management of sickle cell disease because of its potential to bypass the obstruction caused by sickled cells and allow more oxygen to reach the organs and tissues. HRC 101, like some other HBOCs, also has other important advantages over blood transfusions—it can be stored for long periods and doesn’t require a matched blood donor.
The results "are consistent with the hypothesis that HRC 101 augments oxygen delivery to the microcirculation," the researchers write—possibly by increasing the oxygen-carrying capacity of the blood, reducing red cell sickling, and/or bypassing occluded blood flow. Although much more research is needed before human trials can be designed, HBOCs may one day provide a new approach to treatment for patients with sickle cell disease.
While a number of studies of anesthetic drugs in animals have provided useful direction for further research, it is important to note that animal studies are considered basic science and their findings do not always translate to the complex physiological system of human beings.
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