Liquid biopsy company Angle plc, Guildford, UK, has presented positive results from a pilot study to investigate the potential of the company’s Parsortix system to harvest fetal cells from the peripheral blood of pregnant women for the detection of fetal abnormalities.1
In recent years, noninvasive prenatal testing (NIPT) based on a simple blood test for the mother has emerged as the preferred method of testing prenatal fetal health, replacing the traditional but invasive chorionic villi sampling (CVS) and amniocentesis procedures. Over the next year, the UK’s NHS plans to roll out NIPT to women identified as having a high risk of an affected pregnancy.
However, current NIPT procedures have two key limitations. First, NIPT is currently based on the analysis of cell-free fetal DNA (fragments of dead fetal cells), and is limited to testing for chromosomal disorders that are caused by the presence of an extra or missing copy (aneuploidy) of a chromosome. Such disorders include trisomy 21 (Down’s syndrome) and a small number of other very rare conditions. The second limitation is a barrier to entry for companies offering NIPT, as current methods are based on next-generation sequencing (NGS) analysis of cell-free DNA, and the relevant intellectual property rights are tightly held by a few large corporations.
Both of these limitations can be addressed if intact fetal cells (as opposed to tiny fragments of dead fetal cells) can be reliably harvested from the blood of pregnant women. An intact fetal cell opens the potential for whole-genome analysis of the cell, providing complete information on numerous genetic conditions—and not limited to a very small number of conditions.
Related to its Parsortix system, Angle owns granted intellectual property that covers fetal cells as well as cancer cells. Parsortix analysis is based on intact fetal cells—not cell-free DNA—and hence does not infringe the patents related to cell-free DNA analysis held by other corporations. Following an approach from a company in the NIPT space, Angle undertook a pilot study of the capability of the current version of its Parsortix system to harvest and analyze fetal cells from the blood of pregnant women.
“Noninvasive prenatal testing is a major new market for the Parsortix system, and a potential solution to the current limitations of NIPT, providing a more comprehensive diagnosis of fetal abnormalities for mothers at risk of an affected pregnancy,” says Andrew Newland, Angle founder and chief executive. “Angle’s product-based approach to liquid biopsy enables us to leverage partnerships with third parties, which we are developing in the NIPT space, an established and fast-growing large-scale market.”
Angle’s study analyzed the blood of 19 pregnant women processed through the Parsortix system. Large, putative fetal cells were identified in every case. No such cells were found in a similar number of control cases of women who were not pregnant. A test for XY chromosomes was performed whereby if the cells were from a male fetus an XY result would be expected. In 8 out of 19 cases (42%), XY chromosomes were detected, in line with the expectation that around half of the pregnancies would be for a male child.
One blood sample was drawn from a pregnant woman diagnosed with a Down’s syndrome fetus (trisomy 21). In this case, the fetal cells captured by the Parsortix system were found to be positive for trisomy 21. This finding confirmed the potential of the Parsortix system to analyze captured fetal cells for key diagnostic information.
While the results of this small-scale pilot study are considered highly encouraging, further substantial work will be necessary to develop an effective NIPT technology. It is estimated that current cell-free fetal DNA NIPT techniques identify less than 10% of all serious birth defects. A test utilizing intact fetal cells could have much wider application than the current cell-free tests.
Key conditions that were previously investigated by CVS or amniocentesis, but which are not addressed by cell-free fetal DNA testing, include Fragile X, muscular dystrophy, sickle cell disease, spina bifida, thalassemia, and numerous other rare, inherited disorders. Use of Parsortix to capture and evaluate intact fetal cells has the potential to greatly widen the applicability of NIPT, enabling other conditions such as those listed above to be diagnosed using a simple blood test.
For further information, visit Angle.
- Pailhes-Jimenez AS, Denny H, Mumford K, O’Shannessy D. A Novel Method to Enrich and Characterize Circulating Fetal Cells Using the Parsortix Cell Separation System [poster, online]. Poster presented at the annual conference on Advances in Prenatal Molecular Diagnostics, Cambridge, Mass, October 29–30, 2018. Available at: https://angleplc.com/wp-content/uploads/angle-poster-fetal-nipt-29oct18.pdf. Accessed December 18, 2018.
Featured image: The Parsortix PC1 instrument from Angle.