Endometriosis Research: Now and Future Flashcards
What is endometriosis?
Endometrial, uterine lining tissue found outside of the uterus mainly in the pelvis which causes endometrium scarring and is associated with difficulty getting pregnant and pain.
What is the pipeline to making treatments?
Research priorities - any unanswered questions
Patient samples
Patient-specific changes
Cell and animal models
Clinical trials
What is a priority setting partnership?
This involves asking patient, carer and clinician groups together to identify questions which cannot be answered by existing research and produce a top 10 to research and try to increase funding
What type of questions do people want answered about endometriosis?
Things such as how to manage pain, pregnancy, cure, causes etc.
What is the aetiology of peritoneal endometrious?
Changes within the peritoneum of women with endometriosis favor survival of endometrial tissue and establishment of lesions.
What is deep endometriosis?
Nodular disease
What is ovary endometriosis?
Cysts on the ovary
What is retrograde menstruation?
When menstrual tissue goes back into the fallopian tubes and pelvis (this happens in 90% or women) but they don’t know why this sticks in some women and not others.
Why might some retrograde menstruations stick to the pelvic wall?
Change in mesothelial cells lining the peritoneum
How would you investigate the causes of peritoneal endometriosis and what did they find?
Take peritonal fluid from those undergoing surgery and look at the mesothelial cells. They found that the microenvironment in people with endometriosis is altered (there is an increase in metabolism and lactate)
What does an increase in lactate do?
Increases adhesion, invasion and angiogenesis
Can you treat endometriousis by decreasing lactate?
Yes - they repurposed the drug DCA.
How are they testing DCA in cultures?
Putting the DCA in cultured endothelial cells and stromal cells to see what happens. They found that the lactate would be reduced and the stromal cells wouldn’t overproliferate.
How did they check DIC in mice?
They gave a mouse oestrogen in order to make them have a period. They then put this tissue into other mice and saw there was an increase of lactate. They then treated these mice with DCA and the lactate production reduced and the lesions reduced.
What is a single arm, open label exploratory study?
There is no placebo and everyone knows who is getting the drug etc.
What did the singal arm study for DCA show?
They monitored pain and found that pain was reduced, quality of life improved and many people used less pain meds after.
They are now going into a random trial and genotyping (to find fast and slow metabolisers).
How do macrophages influence enodmetriousis?
They are abundant and promote lesions growth and vascularisation and help with the development of pain symptoms. They are found in the pro-repair phenotype and do not pagocytose
Does endometriosis macrophages have the same phenotype as some tumour-associated macrophages?
Yes as these macrophages both promote growth and inhibit phagocytosis however subpopulations exist.
What did their repurposed anti-tumour drug do to macrophages?
Changes into a more inflammatory phenotype and increases inflammasome inhibition, Nrf2 upregulation, macrophage repolarisation, enhanced phagocytosis and vascular normalisation
What did the anti-tumour drug do to the mouse study?
Reduced lesions development, reduced lesion number and size and reduced pain
What study are they in for the anti-tumour drug?
Phase 1 clinical trial
How can cannabinoids be used to treat endometrios?
Could reduce the pain of someone however this can not be scheduled treatment as this is illegal. Also helps reduce lesion size in mice.
What is the endocan-1 clinical trial?
It is a two centre double-blinded randomised controlled canabis trial to look at pain.
What is the later stage clinical trial ran by the NHS?
It is a surgical trial
Why are they doing the surgical trial when surgery is already a treatment?
Some people have good results whilst others do not.
Also there is many different types of endometriosis and this might not be the best treatment for every type.
How can endometriosis be removed?
Cut out (which people veiw as being the best)
Heat, laser ect.
Does surgery completely stop the disease?
No - half of people who have undergone the surgery see a recurrance in under 5 years
What are some complications of the surgery?
Bowel damage etc.
Post surgery can increase chronic pain and neuropathic pain chances.
How is the surgical trail being done?
two groups of women one of which gets a laproscopy to remove the endometriosis and the other to get a laproscopy which will do nothing. They then report all pain management, surgical complications etc for the next 12 months.
Blood is also taken.
What are the challenges of the surgical trial?
This was done during the pandemic so this is specific to that
Sites not having capacity
R&D delays to site opening
Research staff redeployed
Surgical capacity and waiting times
What is happening next in endometriosis research?
Looking at the life process of people with endometriosis as people can get cardiovascular complications and be more likely to develop cancers.
What in ENDO1000
This is a way to support research, diagnosis and treatment by getting people with endometriosis to put their information into their phones, take blood and urine themselves in order to help the researchers.
