Study publication in The Lancet brings with it significant cachet. And Ravgen (Columbia, Maryland), privately held, can make that boast with a study — in an early release online last week in that prestigious journal — of its methods for using genetic markers on fetal DNA recovered from maternal blood.

The study, with accompanying commentary, was completed based on the company’s method of looking at common genetic variants in the human genome, called single nucleotide polymorphisms (SNPs) to determine potential chromosomal abnormalities in the fetus. Ravgen hopes to use that technology in a noninvasive blood test for prenatal diagnosis of disease.

With slightly more than 4 million deliveries in the U.S. annually, there is a greater need for noninvasive methods of screening for genetic abnormalities, according to Ravgen CEO and lead author of the study, Ravinder Dhallan, MD, PhD. Each year, between 150,000 and 200,000 women in the U.S. receive a positive result from screening tests, and at that point women have to decide whether to undergo invasive testing, such as amniocentesis and chorionic villus sampling, which can jeopardize the fetus by potentially causing miscarriage. For that reason, many women avoid this type of testing.

“Our goal is to create a really ideal non-invasive prenatal diagnostic test that’s being used on prenatal DNA with the approach and technology that we’ve developed,” Dhallan told Diagnostics & Imaging Week. He added: “Our goal is to go beyond what is currently being done, because the beautiful thing about the genome and the Human Genome Project being done is it really opens a new era.”

According to Ravgen, it has “long been known” that some fetal cells circulate in the maternal blood during pregnancy, prompting researchers to pursue a prenatal test based on maternal blood. But because it is difficult to separate the small number of fetal cells from the maternal blood, such tests have “remained elusive,” he said.

In the current study in The Lancet, 60 blood samples were taken from pregnant patients — average age 34 — as well as the biological fathers. Ravgen scientists have found a way, using the chemical formaldehyde, to combine with its processing technology to gain a higher percentage of fetal DNA from the maternal blood.

The results of the study showed that the Ravgen methods enabled the direct detection of fetal DNA in the mixture of maternal and fetal DNA, with the average percentage of fetal DNA identified being 34%. Genetic abnormalities can be identified by measuring the number of copies of SNPs on different chromosomes, the company said.

Of the 60 samples analyzed, Ravgen scientists identified three trisomy 21 samples — which are samples that would indicate the presence of Down syndrome — and 57 with a normal copy number of chromosomes 13 and 21.

When these results were compared to amniocentesis or newborn reports, it was determined that Ravgen scientists were correct in two of the three trisomy 21, or Down syndrome cases, and were correct in 56 of the 57 normal cases.

The Lancet commentary says that the company’s approach, that is, that SNPs could be used to determine the number of fetal chromosomes in maternal blood, “is not novel.”

Dhallan disagrees, saying that the company’s research study published in the March 3, 2004, issue of the Journal of the American Medical Association demonstrated its methods.

The Lancet commentary did say that the method Dhallan and colleagues used — quantification and comparison of allele ratio for multiple SNP sties on chromosomes 13 and 21 after fetal DNA enrichment in material plasma — “is original.”

The commentary also suggests that “some technical issues still need to be overcome”; for example, the “amount of free fetal DNA in maternal blood is low (3%-6%)” and “yields are irregular.” The commentary also suggests that further testing will be “essential” in women in their first trimester of pregnancy. Also, it says that “a large number of SNPs are needed for the technique to work.”

As to the need for additional research, Dhallan told DIAG that the company now has a much larger study under way that will prepare the company for an FDA submission, should one be required to commercialize the test. The company is now in the process of researching that.

However, Dhallan pointed out that the company has certification by the College of American Pathologists (Northfield, Illinois), which he called “one of the key steps to be able to process tests in the market.”

Ravgen also points out that the American College of Obstetricians and Gynecologists (ACOG; Washington) in January issued a new Practice Bulletin that all pregnant women, regardless of age, should be offered screening for Down syndrome. Previously, ACOG said, women were “automatically” offered genetic counseling and diagnostic testing for Down syndrome by amniocentesis or chorionic villus sampling only if they were 35 years or older.

From his previous work as an emergency room physician for five years, Dhallan said he learned that “really the first and the most important step in patient care is to be able to diagnose disease.”

He said that the company’s work provides technology “that will allow people to diagnose as much as possible about their baby’s health, so that we can impact the quality of life of that baby at the earliest stage possible.”

And with the findings from the Human Genome Project, researchers ultimately, he said, will be able to diagnose “a much broader array of disorders” that physicians also — ultimately — may be able to treat.