Fetal Hemoglobin Production/Screening

Our company will develop an in vitro tissue culture system which will permit studies of drugs'capability to enhance production of fetal hemoglobin. The Investigator stated that increased fetalhemoglobin in cells of patients with beta-hemoglobinopathy ameliorates the clinical symptoms of theunderlying disease. Several pharmacologic agents have been used to stimulate HbF synthesis duringrecent years. Treatment of patients with 5-azacytidine and hydroxyurea has resulted in higher fetalhemoglobin levels. Despite this, the clinical benefit has not been clearly established. Most agents whichhave been employed are either toxic or have been implicated in carcinogenesis. Therefore there isconsiderable interest in identifying less toxic agents which have potential to increase fetal hemoglobin.Thus far, only a handful of these agents have been tested, mainly due to the lack of an appropriateexperimental system that allows a rapid and accurate determination of the effect on hematologic cells.The Investigator indicates he has recently developed a novel, two-phase liquid culture system forgrowing erythroid progenitors derived from the peripheral blood of normal individuals and patients withhemoglobinopathies. He states that this system has proved to recapitulate in vitro many of thehematologic effects of hydroxyurea in vivo, including the stimulation of fetal hemoglobin production.The purpose of this research is to utilize this methodology for measuring total and fetal hemoglobin. Hewould employ the method for mass screening of agents to determine their fetal hemoglobin stimulatingpotential. The ultimate goal of these studies is to identify drugs with little toxicity which have asignificant potential for stimulation of fetal hemoglobin. He intends to optimize the conditions of theirculture system for stimulation of hemoglobin production and then screen various agents to determinetheir effects. Subsequently, he will use the methodology to study the modes of action of agents whichappear successful in stimulating fetal hemoglobin production.