January 9 2020
A drug designed to tackle diabetes could also be repurposed as the first treatment to prevent miscarriage by targeting the lining of the womb, according to a clinical trial led by Tommy’s National Centre for Miscarriage Research at the University of Warwick.
Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies, with each additional miscarriage decreasing the likelihood of a successful pregnancy. Previous research by the Warwick team found that women who experience recurrent miscarriages do not have enough of a special type of cell in the lining of their wombs: stem cells. These are unspecialised cells that can turn into many other types of cell.
Stem cells and recurrent miscarriage
Many cells in the womb are renewed often, for example after a woman’s period when the lining of the womb regrows. Stem cells are essential in this process. Without them, our body’s tissues age faster – this in turn can cause inflammation that could be harmful to the growing baby, leading to miscarriage.
Researchers identified an enzyme – called DPP4 for short – which they believe is too active in women with a history of recurrent miscarriage. This enzyme can stop stem cells getting from the blood into the lining of the womb.
A new class of diabetes drugs targets this enzyme. The researchers investigated whether reducing this enzyme using this drug, sitagliptin, would increase the number of stem cells in the lining of the womb and improve conditions in the womb for pregnancy.
In a pilot clinical trial, 38 women aged 18 to 42 who had experienced a high number of recurrent miscarriages were given either a course of sitagliptin or a placebo for 3 menstrual cycles. Biopsies of the womb were taken at the start of the course of treatment and afterwards to determine the number of stem cells present before and after the course.
Researchers found an average increase in stem cell count of 68% in those women who took the full course of sitagliptin. This compares to no significant increase in those in the control group receiving an identical placebo pill. They also saw a 50% decrease in the number of ‘stressed’ cells present in the lining of the womb. There were also minimal side effects for the participants.
“We have improved the environment that an embryo develops in and in doing so we hope to improve the chances of a successful pregnancy. Although this research was specifically designed to test whether we could increase the presence of stem cells in the womb, follow-up of participants found that there were no further losses of normal pregnancies in those who took sitagliptin. These are very early results and the treatment now needs to be further tested in a large-scale clinical trial.”
Professor Siobhan Quenby from Warwick Clinical Trials Unit and an Honorary Consultant at University Hospital Coventry and Warwickshire NHS Trust
Stem cells play a key role in creating decidual cells in the womb lining which support the placenta throughout pregnancy. Insufficient stem cells in the womb lining leads to an excess of stressed and inflammatory decidual cells, which in turn may cause placental bleeding and miscarriage. Sitagliptin was effective not only in increasing stem cells in the womb lining but also decreasing the quantity of stressed decidual cells.
“There are currently very few effective treatments for miscarriage, and this is the first that aims at normalising the womb before pregnancy. Although miscarriages can be caused by genetic errors in the embryo, an abnormal womb lining causes the loss of chromosomally normal pregnancies. We hope that this new treatment will prevent such losses and reduce both the physical and psychological burden of recurrent miscarriage.”
Professor Jan Brosens, of Warwick Medical School and Consultant in Reproductive Health at University Hospitals Coventry and Warwickshire NHS Trust
A potential treatment to prevent miscarriage
The researchers now hope to take the treatment to clinical trial and, if successful, it would be the first targeted specifically at the lining of the womb to prevent miscarriage.
“For far too long it has often been said by many health professionals that miscarriage is not preventable, and parents have been left with little hope given the lack of treatment options available. This situation prompted Tommy’s to invest in the Tommy’s National Centre for Miscarriage Research and this breakthrough research by the world leading team at Warwick shows great promise for an effective treatment which will reduce miscarriage and possibly later pregnancy loss too.”
Jane Brewin, Chief Executive at Tommy’s
The research has been published today in the journal EBioMedicine from research conducted with University Hospitals Coventry and Warwickshire and supported by the NIHR Coventry and Warwickshire Clinical Research Facility.
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