In addition to developing Hextend and PentaLyte, BioTime is working in a new field of therapeutic hypothermic surgery, in which the body is chilled to near freezing temperatures and the blood is totally replaced to buy more time for surgeons engaged in complicated procedures requiring the suspension of circulation. The company received a $300,000 research grant from the National Heart, Lung, and Blood Institute to develop HetaCool® as a blood plasma volume expander for profound therapeutic hypothermia.
Dr. Sternberg points out that HetaCool and Hextend are two different products. HetaCool is a version of Hextend used for complete blood volume replacement at very low temperatures. Hextend is used for partial replacement.
“The use of HetaCool calls for the addition of sodium bicarbonate before it is applied to the subject, which enables better buffering capacity and raises the pH to be more suitable for low temperatures and for use without blood,” he explains.
In BioTime’s therapeutic hypothermic experiments at the Texas Heart Institute at the University of Texas Medical School in Houston, animal subjects are cooled to just above freezing. HetaCool is used to completely replace their blood and thus increase the available time in which to perform critical surgeries requiring cardiac and circulatory arrest. The NIH grants called for lowering the body temperature to below 6°C for two hours to prove feasibility. HetaCool could, potentially, be used in high fluid volume procedures in cardiovascular surgery, trauma treatment, and organ transplantation.
It’s too early, however, to speculate on either the time-frame or cost for bringing this product to market. “To the best of my knowledge, we are the only group in the world that has taken primates to just above the ice point for more than one hour and revived them with good neurological outcome,” says Segall.
In the early 1990s, investigators at Barrow Neurological Institute in Phoenix chilled four baboons to as low as 2.5°C deep esophageal temperature and maintained three of them below 10°C using BioTime’s blood substitute from 51 to 137 minutes. During that time, “they were clinically dead,” with no brain activity and no pulse, Dr. Sternberg says.
All animals survived complete blood replacement and profound hypothermia and appeared normal upon gross observation. The baboons were scored according to a 160-point system evaluating motor function, coordination, behavior, and cognitive skills.
All animals that were kept below 10°C received scores of 160/160. However, one baboon who spent only 1 minute below 10°C received a score of 130/160 because the animal did not exhibit the level of aggressive behavior normally seen in baboons.
Complete blood replacement and profound hypothermia appear to be key to achieving neurologic recovery as these baboon studies and subsequent pig studies demonstrate, according to Dr. Sternberg, who admits that many of BioTime’s options are limited by its operating revenues. Grants provide another possible funding option.
In a round of belt-tightening, BioTime employees voluntarily cut their 2005 salaries by nearly $87,000, while the company decreased its general and consulting fees and its investor and public relations expenses by a total of just over $102,000 and cut printing costs by nearly $36,000. Previously, to avoid hiring a CEO upon the death of Paul Segall, the company created the Office of the President, a triumvirate CEO position, filled by Segall, Dr. Sternberg, and Harold D. Waitz, Ph.D., vp of regulatory affairs.
BioTime has made notable inroads but still has a long, uphill battle before it becomes profitable, according to Segall. BioTime was delisted from the American Stock Exchange in 2005. The reason, notes Segall, is that “BioTime did not have the $6 million of shareholders’ equity or the total market capitalization needed to meet the exchange’s continued listing standard, and the exchange no longer has the flexibility to waive its quantitative listing requirements.”
The company’s stock is now traded OTC. According to Segall, an American Stock Exchange spokesperson says the exchange is considering creating a microcap tier, which may benefit BioTime.