Jae Wook Jeong, PhD - Preclinical Modeling of Endometriosis-Associated Pain: Neural Remodeling and Disease Pathophysiology

So we'll talk about some data from our free clinical animal model and what is the potential physiology of the endometriosis associated pain, and then the effect of ovulation of ectopic lesion for the endometriosis associated pain. And I will also introduce one of our new preclinical animal model. So I'm using the heavily used lodent model, but I think the neural entry is too small to apply the free clinical clinical treatment, including the laparoscope. So we developed a few endometrial system there. That's what I will introduce to you. I've never enjoyed the morning session. I think I surprised everybody working together in the same path. And it's also that everybody will nearly understand the field compared to the other disease. And we need to do a lot of things. We need to work together, not one of the genius people can overcome this kind of problem. So I do like to mention introduction of this disease and everybody about its pregnant dependent disease as well dependent projects and involve the chronic inflammatory status and even this regulation and its complicated situation developed the pain.

So we think associated pain. And it's chronic inflammatory conditions. So we want to check the evaluate the potential therapeutic impact of the implement better with focus and IO6 and postprostest signaling pathway because it's even activation and inflammatory lung is definitely elected pain. So what we found was that we've identified the post-processor voluntary activity in the human endometriosis case, collaborating with the doctor oscipas non-human framate model. After we induce the endometriosis, we also identify the first processor level is gradually increased during the endometriosis progression. And we also object the same thing in the rudent mouse model. And from this result, we think that it's potential therapeutic target the endometriosis. So we used to send the ludent model. It induced the endometrial system there, but we combined with the two lupus system. One is the system by luminal sensor. Another one is a fluoresces. So it should make the imaging system in the live energy in the endometriosis progression.

And also it's easy to detect all the small ectopic lesion. So that was the imaging. In the live enemy, we can see the number of the ectopic lesion and size of ectopic lesion. So we have the non-invasive imaging tool and using this GFP technique, so we can identify the small ectopic region and it's very hyper visual radiation and sensitive and past its also the quantitative analysis. We also apply the imaging guide surgery that minimizing the damage for the normal tissue. And this animal model is possible to study about the endometriosis associated in portality and PAL study. And this disease is hormone-dependent disease. We check the hormone dependence of our animal model. And it showed clear that if we treated with condition, it's more ectopic region and if we apply the progesterone its regress.

And first, we want to reach very heterogeneous disease and also the symptom is not matched with the staging system. I think previously it's also the endometriosis related importility. In our model during the stage of the metricist, we do not see any important penotype, but level study we can see the importanty penalty. But important thing is implantation failure and destroy depth is decrease. But even with the same genetic background, the same condition, environmental condition, there are some heterogeneous, some of the mouse have the normal portality. We still struggling that happening signal why that kind of heterogeneous phenotype is.

And now think of endometriosis associated pain. So it's very quality of their life, including walking, clean emotion and imagine value. But in the modern several use of the reflex test, that's not exactly quality of life in the mouth. So we think truly capture the human case. So we think about the monoplex test that is more unlimited human that endometriosis alsociate pain. What we apply for the lesson test lower than to make the less when we give the white blood, because they want to protect the body temperature and also the preparing the pregnancy and the level. But in the mice, it's in complete rule. The last thing scaled this thing, you can see that the endometriosis mice can decrease of the lasting score compared to the mouse.

Mostly they try to hide some of the marble, the material beside behind the nesting. So when we give the seminal marble, the sham mouse try to hide this one inside the building and influence the completely hide we give the high score. If they do not touch the marble, we give zero score. And the same thing also as the high score compared to the endometriosis school mouse. The test is, and as you know, they hide food. When we put the food called inside of the pipe, the diligently and the liver from the inside to the outside, but with the mice endometriosis grow, it's activity also the significant decrease compared to the CHAM animal growth. And so this pain. And we think about the effect of targeting this IN6 and postprostacity and TAFE is the selective inhibitor. It's FDA approved.

And Dr. Have valued the impact of this topatinib in the northern tender metrics model. So objective second contribute in the treatment and the tissue score is improved. The stress treatment we apply same draw to the same impact. I think the side effect is much less tolerant than other diseases, especially our treatment impact or the uterine function that is the bad. So which topology impact the implantation is important function uterine and projects and response, we see that MI is treated with topotinib become the implantation failure. And history showed its implementation failure. So topotinib is endometriosis, but it's impaired the implementation is due to the systemic defect. So we want to think about how to effect this kind of the side effect. So one of the section is the lanoparticle.

Molecule and used for the functional property and it can be used of targeting toxicity and the advantages. It can develop for the diagnostic as well as the drug effect. So nanoparticle how to work is the three molecules diffused everybody, but the non-cytritus is endometrial region. It's developed angiogenesis, but it's some abnormal angiograms we call the enhanced permeability and retention effect. Some of genesis can access to the ectopic region in which to the lymph area. And we use that one as the algorithm because algorithm is not a harmful protein and we conjugate ICG for the diagnosis and nanocellular is the anti-inflammatory molecule. That's what we applied. So that is the non-particular structure, especially one of the important characteristics shift from M1 to M2 anti-inflammatory condition and that is.

And we ask the impact of the small particle for the targeted drug delivery and second measure diagnostic using the RA in vivo emerging and so the data flick effect. So we see the first drug effect and it progresses data show that it's accumulated in the ectopic medium, but the retrophic area is much less than the ectopic area. And from the histological analysis that spot represent the ICG nonparticle, so we can see that it's accurate topic vision, but it's difficult to detect. And mostly importantly, after treatment data with the nonparticle, the mouse has no harmful implantation and histological data also isshomen and also using the polychostic imaging system, we can identify that it's exactly the ectopic region in the live animal after the flow we dissect animal and which the data is exactly correlated with the data. And also as the data field impact, as you can see the effect of the IS examples for testing inhibitor, we also see the sequential reduction of the ectopic lesion.

And the most important thing is non-practical initiative area is last four dose, we can see the similar effect and validate that factor using the expression of postprostest limb and that data show the test reactivation is a major course of the estrogen dependent inflammation and diagnostic non-cell or normal anti-inflammatory nanoparticle provide the promising approach for the endometriosis treatment. And one thing is real focus targeting the ectopic region and from this meeting and several clinician and basic scientists said the endometriosis is a systemic disease. So we ask a question for selective mention of ectopic region is sufficient to elevate endometriosis associated pain. So what we did was that we applied, I think that system. So after reinduce the endometriosis, they have the behavior defect with the ectopic region and then the pain of social behavior and additional SM fibrosis. So that is how the system is rare, genetically engine model cell ever express the projects in the sector.

And then if we treat it with the toxin or the protest positive cells die, which has effect using the using the quantitative analysis. And we also check the perceptor of the PI positive cell after deep toxic evaluation. So you can see that it's completely deleted all the endometrial stroma cell. And so we compromise, we apply this technique to the animal model after endometrial cyst induction and apply the PSN viral test, which is the endometriosis group show that compared to the and the toxic group includes improve some of this defect, but it's very partial effect. And we confirm that all the ectopic lesions are overlated after we express the experimental and then we also confirm all of the post PR and post testing all of the disregulated molecule reconfirm it's all gone. And then we think one of the thing is that the tissue of the region level observe in the element water.

At all the ectopic lesion, we still see the severe tissue lesion. So that is the water and the histology, you can see the wing lesion, it's all attached to the uterus and just the lesion. I think this is in testing. After the lesion, the lesion is grown, but the tissue still have the tissue lesion and we check the fibrosis is one of the region to make the tissue lesion and the induced pain. So that's why we apply the check fibrosis. We can see that all the regions are gone, but still exist fibrosis in the legion and we come from the target protein, and we can see that back of the fibrosis loaded protein that still existed near the region after the evaluation. And that's obviously, and I think I will just introduce our slide model. We published this model. There are several different model system to study the.

I think the relevant model, I like it. And some people I think depend on which as the question answer we need to apply. One of the limitation of the valve model is size, the body is the human care is 2,500 high than the Y. And then the important is we can offer the clinical equipment scopic system system and the reinduced materials. We can see the same concept, but if we can label the ectopic using the similar to the human and the advantage of this animal model is we can identify the productive legion. And in this generality, the progress GFP transgender peak without any labor, we can see the oil and ventrum health expressed the GFP signaling and rule apply the same thing that's the laparoscopic imaging in this one that is very similar about advantages express the GFOP and histologically it's similar to the human.

I think this model will go for study the deep implementing endometriosis. It's impossible to generate those data and I also need to appreciate my funding source.