Researchers are stepping up efforts to develop a safe blood substitute amid a growing demand and dwindling supply of the real thing to treat trauma victims and blood disorders such as potentially deadly types of anemia.
Their major hurdle: to come up with a replacement for hemoglobin (an iron-enriched protein in red blood cells that transports oxygen from the lungs to the rest of the body) that can be directly introduced into the human circulatory system. The problem is that the body breaks down and eliminates real hemoglobin that is not protected by red blood cells, a process that can be toxic to the kidneys, constrict blood vessels (resulting in hypertension), and cause inflammation.
The Texas Tech University Health Sciences Center in Lubbock and Dallas-based blood substitute developer HemoBioTech, Inc., believe they have a chemically modified bovine hemoglobin called HemoTech that not only suppresses hemoglobin's inherent toxicity but also serves to improve blood flow and even spur the creation of new red blood cells. "This represents a learning from all of the failures that have proceeded us over the past 35 years," says Arthur Bollon, HemoBioTech's chairman and chief executive officer. Texas Tech University spun off HemoBioTech in 2002 to commercialize HemoTech.
"Creating an effective substitute for human blood has been an elusive dream for many decades," says Jan Simoni, associate research professor in Texas Tech's surgery department and HemoBioTech's acting vice president for research and development. "Our product addresses all the intrinsic toxicity issues."
HemoBioTech's use of modified bovine hemoglobin addresses the two biggest issues affecting today's blood supply: There is not enough to go around and the available blood runs the risk of contamination. "Bovine hemoglobin is an unlimited source of raw material for making blood substitutes," Simoni says. Hemoglobin from bovines (which include antelopes, bison and cattle) also does not carry human-born viruses such as HIV and hepatitis. It could, however, potentially carry other pathogens that might be transmitted to humans, such as the protein that causes mad cow disease. But Simoni says Texas Tech scientists have developed a method to effectively filter out such threats.
He adds that real blood must be carefully screened, noting that one in every 60,000 units may carry hepatitis B and one in every 500,000 units, HIV; other contaminants of concern are hepatitis C and the human T-cell leukemia virus.
"The World Health Organization estimates that 100 million units (45 million liters) of blood are needed worldwide per year," Simoni says. "There are not enough blood donations to meet the demand when you consider that the demand is increasing by 1 percent per year, while donations are decreasing by 1 percent per year." The U.S. alone annually uses about 12 million units, and by 2030 it is projected that there will be a shortage of as much as four million units of blood.
HemoTech also eliminates the need to match blood types between patients and donors, because pure hemoglobin is not affected by varying factors found in human blood. In addition, HemoTech has a shelf life of at least 180 days—significantly longer than the typical 42-day period during which donated blood can be used.
In the early 1990s HemoTech was used in Zaire to successfully treat nine children with sickle-cell anemia. In fact, HemoTech constituted 25 percent of each patient's blood volume during the treatment. None of the patients suffered toxic side effects, Bollon says.
But it could be years before the product is approved for other than experimental use. HemoBioTech is in the process of obtaining permission from the Food and Drug Administration (FDA) to conduct clinical trials in the U.S. The company hopes that early next year it will initiate clinical trials on product safety, which will pave the way for human efficacy testing that could be completed by 2011. Clinical trials are set to begin in India early next year. If all goes according to plan, HemoTech is expected to be a cheaper alternative to treating patients with donated red blood cells.
While HemoBioTech is not alone in its quest to create a blood substitute, others have run into difficulty during clinical testing. Northfield Laboratories, Inc., in Evanston, Ill., has been conducting clinical trials for its oxygen-carrying red blood cell substitute, PolyHeme, but in May said the product failed to meet the primary goals of mortality and safety in an important phase III study. Biopure Corporation in Cambridge, Mass., is working on FDA approval for its "oxygen therapeutics," which are intravenously administered to deliver oxygen to the body's tissues, after the agency in July 2005 put the company's clinical trials on hold, citing safety issues. Last month, Biopure launched a revamped clinical development program, emphasizing testing in Europe, with three phase II clinical trials planned for 2008 to study the impact of its product on heart attack patients, chemotherapy patients with anemia and the terminally ill.
Another blood substitute provider, Synthetic Blood International, Inc., in Costa Mesa, Calif., has thus far successfully navigated the clinical trial waters with Oxycyte, an oxygen-carrying intravenous emulsion that the company says can carry up to four times more oxygen than hemoglobin. In May, Synthetic Blood announced its phase II study in patients with traumatic brain injury indicated Oxycyte helped increase blood oxygen levels.
Although there is no guarantee that any of these blood substitutes will make the grade, each holds the promise of bringing relief to the health care organizations and their patients that rely on rapidly declining supplies of donated blood.