IVD Technology Magazine | IVDT Article Index
Originally published March 1996
Pace picks up for fetal genetic test from maternal blood
Scientists debate means, efficacy of osteoporosis assays
With estimates of millions of dollars in profits looming, several companies say they are close to hatching a simple maternal blood test to determine the genetic health of an unborn baby. But experts in the field warn that those on-the-brink announcements have been going on for some time now, and that the problem of harvesting substantial quantities of fetal cells from the mother's blood has yet to be solved.
"Most tests I am seeing are very cumbersome," says John Stone, PhD, a geneticist at Genetrix (Scottsdale, AZ) who has been following the developments. He predicts that, with luck, commercial availability will coincide with the turn of the century. However, clinical trials are already being conducted at Tufts University School of Medicine in Boston.
Johnson & Johnson Clinical Diagnostics, Ltd. (Amersham, UK), has provided technical assistance and a small grant for cell-enrichment research by Bioventures, Ltd. (Leeds, UK), a spin-off of the department of clinical medicine at Leeds University. Scientists there seek to develop a technique to separate fetal erythroblasts, which circulate in maternal peripheral blood within weeks of conception, from maternal erythroblasts. The sorting rests on detection through use of monoclonal antibodies or other types of probes.
Applied Imaging (Santa Clara, CA) has developed an automated system for analyzing marked cells alongside the patented fluorescent-labeling technique. Theoretically, venipuncture could yield enough cells to do an accurate chromosome profile, but without concrete proof of their numbers by means of other suitable markers the detection of these cells "cannot be accepted as evidence of their fetal origin," asserts Matteo Adinolfi, MD, of the Department of Genetics and Biometry at London's University College, in a review article that appeared last fall in the journal Prenatal Diagnosis. In fact, some investigations are now focusing on quantifying fetal cells by a method that uses polymerase chain reaction to test for sample purity and document recovery. Integrated Genetics (Framingham, MA) has been on the cutting edge of this research.
None of the companies believed to be closest to a marketable product are forthcoming about the process being used. Most companies "lack a system of enrichment" that would provide high enough amounts of fetal cells for a truly confident result, says Donald Payne, vice president of finance for Aprogenex, Inc. (Houston). The Aprogenex kit uses DNA probes that identify the cells by detecting the fetal hemoglobin messenger RNA and targeting specific chromosomes. The kit has proven effective in picking up abnormalities like trisomy.
Payne declined to reveal Aprogenex's list of corporate buyers, but he acknowledges that even though the Aprogenex kit is being used, it is still "under development" due to the "fetal-cell enrichment problem." Payne believes the Aprogenex test could be performed at 1020 weeks gestation and, with refinement, could render chorionic villi sampling and amniocentesis obsolete.
Applied Imaging has developed and patented a fetal cell enrichment procedure (see Figure 1). The system also includes an automated scanning and relocation instrument and DNA probes for enumerating the chromosomes of interest.
The clinical trials on the technique have so far taken place abroad. Applied Imaging currently has testing under way in Holland and expects to begin marketing its system--which employs a different hematologic approach that makers do not want to describe--across Europe this year. "We believe whoever is first with this has a definite strategic advantage," says Abe Coriat, chairman of the board at the company.
Researchers point out in recent articles in Prenatal Diagnosis that this kind of technology will have to have a pristine and stellar track record before it will come into wide use. A less invasive method would be free of the shortcomings of the two present methods, which both carry a slight risk of miscarriage. However, in fetal medicine, false negatives and positives are seen as nothing short of tragic. The method will be used alongside current techniques until its sensitivity and specificity are proved beyond the shadow of a doubt. --Anne Scheck
