Bone marrow suppression is a major clinical problem in treating cancer and AIDS patients, resulting in opportunistic infections (suppression of white blood cell production) and hemorrhaging (suppression of platelet production). Clinical trials have shown the safety and effectiveness of administering blood cell growth factors and cytokines to stimulate the bone marrow. However, they are very expensive and they are not orally active. There is opportunity for a compound that can be chemically synthesized and perhaps taken by mouth to capture a share of the potentially large market for stimulators of granulopoiesis (various financial analysts estimate that this will be a 1 billion dollar market by 1994 with an upward potential of 3 to 5 billion dollars in worldwide sales by the year 2000). One promising source of such compounds is a traditional Chinese medicine, Cordyceps sinensis, tonics of which increase cancer patients' tolerance of high-dose chemotherapy. During the Phase I period, extracts of this material have been found to stimulate hematopoiesis in vitro. The stimulant appears to act indirectly on the hematopoietic cells by stimulating adherent cell populations in the marrow to secrete stimulatory cytokines. It has no direct effect upon hematopoietic progenitors. The biochemical characterization of the stimulant showed that it is very amenable to purification and characterization. These data illustrate the feasibility of isolating bioactive compounds from the extracts. Because of its lack of toxicity in vivo and its administration by mouth in China, these data suggest that this fungus may contain a natural product whose isolation could lead to orally-active stimulants of human hematopoiesis. The stimulant also seems to share some characteristics with endotoxin, yet it reportedly is not toxic even at high doses in mice and humans, further suggesting that the stimulant may also serve as a starting point to develop endotoxin analogues that could be used to antagonize endotoxin binding or activity and thereby prevent endotoxic shock.
