Prenatal diagnosis by a simple blood test instead of amniocentesis wasdescribed in Paris last Friday to the 26th annual meeting of theEuropean Society of Human Genetics.William Weber, laboratory manager of Aprogenex Inc., told theconference how his company's DNA probe technology can single outfetal cells in a small sample of maternal blood, and analyze theirchromosomes for the most common genetic abnormalities. (SeeBioWorld Today, Feb. 18, 1994, p. 3.)Weber titled his presentation, "Non-Invasive Prenatal Diagnosis UsingFetal Nucleated Red Blood Cells Isolated From Maternal Blood: AFeasibility Study." The assay, which the Houston-based company calls"GenSite," picks out the rare fetal red blood cells that still containnuclei and bind to the messenger RNA of their hemoglobin by in situhybridization. It also enumerates chromosomes to be analyzed. (FetalmRNA differs in its molecular chain structure from that of adulthemoglobin.)Last month, Aprogenex introduced U.S. clinicians to its impendingtest, at the annual meeting of the American College of Obstetrics andGynecology.Weber reported here an in vitro trial of the system in which fetal cellswere identified in peripheral blood from pregnant women, and probedfor the X and Y sex-determining chromosomes. Fetal sex andchromosome profiles agreed with amniocentesis findings.No cells from 10 controls _ five non-pregnant women and five males_ hybridized with the mRNA fetal hemoglobin probes."This system," Weber concluded, "will safeguard against thepossibility of misdiagnosis on samples from women carrying femalefetuses."Aprogenex also presented two posters at the Human Genetics Meetingon Thursday. They described the rapid isolation of fetal cells frommaternal blood, and chromosome enumeration techniques.Current tests, by amniocentesis or chorionic villae biopsy, involvetapping the mother's abdomen to withdraw aminiotic fluid, or biopsythe placenta, for fetal cells, then culturing these to detect chromosomalanomalies. Although reliable and safe, amniocentesis does entail a one-in-200 risk of miscarriage, Aprogenex's vice president of finance,Donald Payne, told BioWorld Today."Conceptually," Payne said, "our probe technology should eventuallyreplace amniocentesis." But in its initial commercialization phase, headded, GenSite will be marketed as a screening test, with amniocentesisrecommended to confirm positive findings of potential genetic defects."Cost-benefit work," he said, "indicates that our widespread screen canactually save lives and costs, and lower the number of amnios."He estimates that the Aprogenex probe "will cost a patient about one-third or less" of current prenatal diagnosis pricing by amnio. Its in situhybridization can be completed in an hour, rather than overnight bypresent methods.The company's president and CEO, Joel Bresser, is first inventor ofU.S. patent number 5,225,326, issued July 6, 1993. The patent claimsits one-step in situ hybridization "may be accomplished in 5 minutes to4 hours."Payne expects Aprogenex to seek FDA approval by the third quarter ofthis year of its fetal-cell assay, now in pivotal clinical trials, as adiagnostic device. Marketing in Europe and China should begin by theend of the year.He said that Genzyme Corp and CellPro Inc., of Bothell, Wash., aredeveloping competing systems, based on monoclonic antibodydetection of fetal cells, but that neither has yet advanced to clinicaltrials.William Braun is vice president and program manager for fetal cell testdevelopment program at Genzyme/ Integrated Genetics, inFramingham, Mass.Apropos Payne's comment, he told BioWorld Today, "This includesmonoclonal antibodies as well as other methods for detection of fetalcells. We have our own in situ hybridization technology," Braun added,"which we are now modifying for use on fetal cells found in maternalcirculation." He confirmed that his program has not yet undertakenclinical trials."Genzyme has already spent over $24 million in this field," Braun said,"and holds exclusive rights to the overriding patent on use of fetalnucleated red cells." n
-- David N. Leff Science Editor
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