Endometriosis Research: Now and Future

Question 1

What is endometriosis?

Answer 1

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.

Question 2

What is the pipeline to making treatments?

Answer 2

Research priorities - any unanswered questions

Patient samples

Patient-specific changes

Cell and animal models

Clinical trials

Question 3

What is a priority setting partnership?

Answer 3

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

Question 4

What type of questions do people want answered about endometriosis?

Answer 4

Things such as how to manage pain, pregnancy, cure, causes etc.

Question 5

What is the aetiology of peritoneal endometrious?

Answer 5

Changes within the peritoneum of women with endometriosis favor survival of endometrial tissue and establishment of lesions.

Question 5

What is deep endometriosis?

Answer 5

Nodular disease

Question 6

What is ovary endometriosis?

Answer 6

Cysts on the ovary

Question 7

What is retrograde menstruation?

Answer 7

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.

Question 8

Why might some retrograde menstruations stick to the pelvic wall?

Answer 8

Change in mesothelial cells lining the peritoneum

Question 9

How would you investigate the causes of peritoneal endometriosis and what did they find?

Answer 9

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)

Question 10

What does an increase in lactate do?

Answer 10

Increases adhesion, invasion and angiogenesis

Question 11

Can you treat endometriousis by decreasing lactate?

Answer 11

Yes - they repurposed the drug DCA.

Question 12

How are they testing DCA in cultures?

Answer 12

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.

Question 13

How did they check DIC in mice?

Answer 13

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.

Question 14

What is a single arm, open label exploratory study?

Answer 14

There is no placebo and everyone knows who is getting the drug etc.

Question 15

What did the singal arm study for DCA show?

Answer 15

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).

Question 16

How do macrophages influence enodmetriousis?

Answer 16

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

Question 17

Does endometriosis macrophages have the same phenotype as some tumour-associated macrophages?

Answer 17

Yes as these macrophages both promote growth and inhibit phagocytosis however subpopulations exist.

Question 18

What did their repurposed anti-tumour drug do to macrophages?

Answer 18

Changes into a more inflammatory phenotype and increases inflammasome inhibition, Nrf2 upregulation, macrophage repolarisation, enhanced phagocytosis and vascular normalisation

Question 19

What did the anti-tumour drug do to the mouse study?

Answer 19

Reduced lesions development, reduced lesion number and size and reduced pain

Question 20

What study are they in for the anti-tumour drug?

Answer 20

Phase 1 clinical trial

Question 21

How can cannabinoids be used to treat endometrios?

Answer 21

Could reduce the pain of someone however this can not be scheduled treatment as this is illegal. Also helps reduce lesion size in mice.

Question 22

What is the endocan-1 clinical trial?

Answer 22

It is a two centre double-blinded randomised controlled canabis trial to look at pain.

Question 23

What is the later stage clinical trial ran by the NHS?

Answer 23

It is a surgical trial

Question 24

Why are they doing the surgical trial when surgery is already a treatment?

Answer 24

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.

Question 25

How can endometriosis be removed?

Answer 25

Cut out (which people veiw as being the best)
Heat, laser ect.

Question 26

Does surgery completely stop the disease?

Answer 26

No - half of people who have undergone the surgery see a recurrance in under 5 years

Question 27

What are some complications of the surgery?

Answer 27

Bowel damage etc.
Post surgery can increase chronic pain and neuropathic pain chances.

Question 28

How is the surgical trail being done?

Answer 28

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.

Question 29

What are the challenges of the surgical trial?

This was done during the pandemic so this is specific to that

Answer 29

Sites not having capacity
R&D delays to site opening
Research staff redeployed
Surgical capacity and waiting times

Question 30

What is happening next in endometriosis research?

Answer 30

Looking at the life process of people with endometriosis as people can get cardiovascular complications and be more likely to develop cancers.

Question 31

What in ENDO1000

Answer 31

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.