Heavy menstrual bleeding, abdominal pain and infertility – benign growths in the uterine muscles can take a substantial toll on affected women. Bayer researchers are collaborating with the renowned University of Oxford to offer new therapies for patients.
Uterine fibroids are tumors that are usually benign, but they still cause severe symptoms in many patients. Existing therapies have substantial side effects.
Using state-of-the-art methods, researchers from Bayer and Oxford University are investigating the genetic causes of fibroid disorders. Using their findings as a basis, they can identify substances that could be candidates for future active ingredients.
More than one in four of all patients with uterine fibroids suffers from heavy bleeding and abdominal pain. New drug products may be able to relieve these symptoms - with fewer side effects than conventional hormonal therapies or surgery.
When cells take on a life of their own and elude the body’s control mechanisms, tissue begins to grow unchecked and, over time, this leads to the development of a pathological growth. A minor yet vital behavioral detail is responsible for determining which path the tumor will ultimately take – to become either a benign tumor or a malignant one. Malignant tumors infiltrate adjacent tissue and organs and form metastases. Benign tumors, on the other hand, remain at their place of origin, growing uncontrollably and harming adjacent tissue, and frequently leading to disrupted bodily processes.
Take uterine fibroids, for example: In this type of tumor, cells grow unchecked in the uterine muscles. “Up to three quarters of all women have such fibroids later on in their reproductive years,” explains Professor Krina Zondervan from the University of Oxford, whose research group is examining the impact of genetic and environmental factors on women’s health. The majority of women don’t even notice these benign tumors, but one in four women experiences intense symptoms such as heavy menstrual bleeding and abdominal pain.
“These women require medical treatment, but we currently don‘t have very many therapeutic options,” says Zondervan. There are basically two ways of treating fibroids: One common method involves medicines that act like hormones and cause the growths to shrink. The other approach is an operation to surgically remove the tumors. However, both methods can cause serious side effects, and the fibroids recur in the long term in the majority of patients.
Using omics methods to track down disease causes
To be able to effectively treat a disease, scientists have to understand how it develops. This is difficult in areas where little is known about the condition, as is the case with uterine fibroids.
One way of changing the situation is by using omics methods. Here, scientists analyze all of one class of molecules in a sample, for example, the genes, in which case they refer to it as genomics. This approach can also be applied to many other types of molecule, for example transcripts, working copies of the genes for cellular metabolism, or proteins, the molecules that make possible most of a cell’s functions from its structure through to its metabolism in the first place. Researchers refer to these methods as transcriptomics and proteomics respectively. This methodology can also analyze all metabolic products. In some cases, the researchers are able to compile the data automatically, and all relevant information is then fed into the computer for evaluation and combination, helping scientists to better understand the origins of the disease. In ideal cases, they are then able to intervene with drug therapy before complications arise.
“We are working together with specialists from the University of Oxford so that we can combine our expertise and develop entirely new strategies,” explains Dr. Thomas Zollner, head of Gynecological Research at Bayer Pharmaceuticals. The research partnership for women’s health was formed in 2014. “Since then, we’ve already identified a double-digit number of novel mechanisms and new active substances,” reports Dr. Joerg Mueller, laboratory head in Gynecological Research at Bayer. Over the past years, he and his colleagues have focused their efforts on endometriosis.
“Now we are primarily concentrating on polycystic ovarian syndrome (PCOS, see research 30) and uterine fibroids, and have decided to, among other things, pursue a systems biology approach,” adds Zondervan. This decision was partly based on the fact that the researchers were unable to find many existing publications with detailed information about fibroids and how they cause heavy menstrual bleeding. Therefore, the scientists‘ initial focus is on examining the fundamental aspects of the disease. For example, they are seeking to understand the role that patients’ genes play in the pathogenesis. The specialists are therefore using what are referred to as integrated omics methods to conduct high-throughput analysis of tissue samples stemming from affected women. “Direct and close cooperation with patients is one of the University of Oxford‘s great strengths,” says Zollner, explaining how this contributes a wealth of expertise from clinical routine and access to many cell samples.
Up to 30 percent of all women with uterine fibroids experience symptoms.
Source: Williams, 2017, F1000 Research
In a second project, the researchers are focusing on how blood vessels supply the fibroid tumors. “This is a crucial step in the emergence of such cell constructs,” says Zollner. Regardless of whether a tumor is benign or malignant, “More cells require more nutrients – and these are supplied through the bloodstream,” Zollner explains. “We’d like to cut off this supply route in a tissue-selective manner.”
The researchers have since identified several promising substances that could help women with uterine fibroids in the future. “These molecules face a long and arduous journey on the path to becoming an approved medication,” says Mueller. There are only very few substances that make it to the final phase of being registered as a drug product. “That’s why it’s so important for us to continue our research so that we can send several promising molecules on this journey,” Zollner emphasizes. Earlier this year, the term of the collaboration with the University of Oxford was extended until June 25, 2022. As Zondervan is well aware, “We still have a lot of work to do, through 2019 and beyond, before we can offer new therapeutic options for women with uterine fibroids.” However, thanks to the work that has already been conducted, the research community knows much more about the causes of the disease than it did before the launch of the partnership.
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