Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pilot study suggests new approach to treat preeclampsia

03.08.2011
Apheresis-based treatment reduces elevated levels of placental factor and may prolong pregnancy

A novel therapy that reduces elevated blood levels of a potentially toxic protein in women with preeclampsia, a dangerous complication of pregnancy, may someday address the therapeutic dilemma posed by the condition – balancing life-threatening risks to the mother with the dangers that early delivery poses to an immature fetus.

In a paper receiving online release in the journal Circulation, a team of U.S. and German researchers report promising results from their pilot study of a filtration technology that reduces reduce excess blood levels of soluble Flt-1, a protein that limits the growth of blood vessels, in women with very preterm preeclampsia.

"Introducing new therapies in pregnancy is uncommon because of the need to avoid extra risks to both the mother and baby," says Ravi Thadhani, MD, MPH, of the Massachusetts General Hospital (MGH) Division of Nephrology, co-corresponding author of the report. "In this paper we show that a disease that affects thousands of women around the world may one day be able to be managed by the therapy we developed. This was a small, proof-of-concept study to see if the therapy is safe and possibly effective; so larger, randomized trials now need to be done."

Affecting 5 to 7 percent of pregnancies, preeclampsia is characterized by high blood pressure, protein in the urine and additional metabolic abnormalities. If symptoms progress, it can lead to kidney or liver failure, brain swelling, seizures and death. Since the only way to halt the process is to deliver the fetus, the earlier in a pregnancy preeclampsia occurs the greater the risk to the baby. Very preterm delivery – before 32 weeks of gestation – has been estimated to increase infant mortality as much as 70 times over full-term delivery at 37 or more weeks. Very preterm babies who do survive may face lifelong complications such as cerebral palsy, so finding an intervention that can safely prolong pregnancy is vitally important.

The underlying cause of preeclampsia is still unknown, but one hypothesis is that factors released into the bloodstream by the placenta damage blood vessels throughout the body. In a 2003 study Ananth Karumanchi, MBBS, of the Beth Israel-Deaconess Medical Center, a co-author of the current study, identified soluble Flt-1 (FMS-like tyrosine kinase 1) as a possible factor in preeclampsia. Released by the placenta and other tissues, soluble Flt-1 blocks the vascular growth factor VEGF, which is essential to maintaining healthy blood vessels; and levels of soluble Flt-1 are extremely elevated in women with very preterm preeclampsia. Developing a preeclampsia treatment based on removing a factor like soluble Flt-1 rather than giving a drug that may have side effects of its own presented an attractive strategy.

Thadhani and his colleagues adapted the blood-filtering technologies used in apheresis to develop a method of rapidly removing soluble Flt-1 from the bloodstream. Since a blood test to measure soluble Flt-1 levels is available in Germany, Thadhani collaborated with Thomas Benzing, MD, University of Cologne, co-corresponding author of the Circulation paper, and Holger Stepan, MD, of University Hospital Leipzig, on the pilot clinical study. The first phase was designed to confirm the safety of the treatment and determine whether how long it was administered affected how much soluble Flt-1 was reduced. In five patients with very preterm preeclampsia and elevated soluble Flt-1, levels did drop in response to a single treatment, with a greater decrease associated with longer treatment. There were no major side effects, but because the treatment sessions were brief, no extension of pregnancy was expected or seen.

The researchers then offered three women with very preterm preeclampsia – from 27 to 30 weeks – the opportunity to receive several treatment sessions in an attempt to extend their pregnancies. Two patients, one of them carrying twins, received two treatments; and the third received four. After each treatment session, the patients' soluble Flt-1 levels dropped from 20 to 30 percent for several days and urinary protein levels also dropped. Various factors, including recurrence of preeclampsia symptoms, eventually required premature delivery of the babies; but the pregnancies had been maintained from two to three weeks after hospital admission. A comparison group of patients that received standard monitoring required delivery an average of 3.6 days after admission. While the babies of women receiving the novel treatment needed the type of support typically required for premature infants, they all were discharged from the hospital with few complications.

"There has never been an effective therapy for this condition," says Thadhani, an associate professor of Medicine at Harvard Medical School. "We've been working for over a decade to find ways to extend the baby's time in utero while preventing the rapid acceleration of preeclampsia that can take a mother from feeling fine to a coma in a matter of hours. One of the beauties of an approach based on removing something instead of giving a drug is that it can be carefully controlled and, if necessary, quickly turned off. While this study is too small to allow us to say that our treatment was responsible for extending these patients' pregnancies – that will require a larger, randomized clinical trial – this first step holds promise."

Support for the study includes grants from the Discovery Fund of the MGH Department of Medicine, and from the University of Cologne and Howard Hughes Medical Institute. Thadhani and co-author Karumanchi hold patents related to preeclampsia prediction and the use of angiogenic proteins in preeclampsia, respectively. Additional co-authors of the Circulation paper are Tuelay Kisner, MD, Henning Hagmann, MD, Verena Bossung, MD, Stefanie Noack, RN, Peter Mallmann, MD, Angela Kribs, MD, and Oliver Cornely, MD, University of Cologne; Wiebke Schaarschmidt, MD, Alexander Jank, MD, Clauria Kreyssig, MD, and Tom Lindner, MD, University Hospital Leipzig; Linda Hemphill, MD, MGH Division of Nephrology; and Alan Rigby, PhD, and Santosh Khedhar, PhD, Beth Israel-Deaconess Hospital.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital (www.massgeneral.org) is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, reproductive biology, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>