Current Research on Endometriosis: An Interview with Prof. Caroline Appleyard

Teresa Götz: Could you please introduce yourself briefly?

Prof. C. Appleyard: My name is Caroline Appleyard. I am a professor in the Department of Basic Sciences at Ponce Health Sciences University, Ponce Research Institute on the south coast of Puerto Rico. In addition to having a research lab there, I also direct a couple of graduate training programs.

Teresa Götz: How did you come to research endometriosis?

Prof. C. Appleyard: This is a bit of a longer story because before I moved to Puerto Rico, I was very involved with researching gastrointestinal inflammation. I was very interested in inflammation of the gastrointestinal tract and diseases like ulcerative colitis and irritable bowel syndrome. However, when I came to Puerto Rico, it was a smaller research facility, so it was more of a multidisciplinary environment. There I met Dr. Idhaliz Flores, who is now a very good colleague and friend and works a lot with patients in endometriosis research. In many conversations with her, it became clear that there are many similarities and possibly differences between some gastrointestinal disorders and endometriosis. At the time, I was also very interested in the brain-gut axis and how it can affect gastrointestinal disease. That eventually led to a collaboration with us and a neuroscientist, Dr. Kenira Thompson, which led to us getting funding to study the effects of stress in endometriosis and to compare animal models of intestinal disease with what’s going on in endometriosis.

Teresa Götz: What fascinates you most about this topic? What is your main motivation?

Prof. C. Appleyard: I think the main factor is its very interdisciplinary. It’s very interesting to me that it’s very multidisciplinary research and that there’s so much overlap between endometriosis and other chronic diseases. There is a possibility that in the future, especially recently, that there will be more awareness of how the environment can impact these chronic diseases and that we can find new, complementary approaches to help patients specifically with endometriosis, but potentially with other chronic diseases as well. One of my biggest motivations, as I mentioned earlier, is the fact that I work in a small facility that is a very collaborative team. We have a really good collegial environment and the fact that we have different backgrounds. I’m a clinical pharmacologist by training, but I now consider myself an animal physiologist in some ways. Dr. Idhaliz Flores has a molecular biology background. We also work with neuroscientists such as Dr. Annelyn-Torres-Reveron and the various psychologists on our team.

I think this area is finally getting a little more attention, and that’s through community involvement and a lot of groups and patient communities.

Teresa Götz: What do you think is the biggest challenge in the field of endometriosis right now?

Prof. C. Appleyard: There are a lot of different challenges. I would say one of the biggest continues to be the fact that awareness needs to be raised about how much this disease – as well as other chronic diseases – can affect women, who make up a large part of the workforce. The disease really affects all aspects of daily life. I think that for a long time, women were not taken seriously; they had to put up with it. I’ve heard this anecdotally many times. I know students and colleagues who have this disease. It’s terrible that it’s taken so long for awareness of this disease to grow, but I think it’s growing. I would say that there is still a need that maybe has to do with the fact that it takes so long for the disease to be diagnosed. I think it’s still a challenge to develop newer, better imaging techniques and non-invasive biomarkers so that we can try to detect the disease earlier so that we can offer treatment to patients. Another challenge that I’m particularly interested in is standardizing the animal models that we use because if we’re going to translate what we’re trying to do in the research lab into new therapeutics or other approaches, we need to make sure that those animal models are relevant and can help with that aspect of translation.

Teresa Götz: Could you perhaps explain the study you presented at the World Congress on Endometriosis or your broader research?

Prof. C. Appleyard: As I mentioned earlier, I am very interested in the brain-gut axis and interactions. We know that stress plays a big role in many different chronic diseases. When we first started getting interested in this area, there was only anecdotal evidence that stress could exacerbate endometriosis. We know that endometriosis itself causes a lot of stress as patients struggle with the pain, symptoms, and infertility. We hypothesized that the stress would make the disease worse, and if we could control the stress, maybe the disease would improve. At that point, there was no conclusive research on the subject, so we started working in animals. We did this by exposing the animals to a stressor either before or after endometriosis induction. We could see that the signs of endometriosis worsened in the animals, so we had more and larger lesions. What was even more exciting for us was the fact that this could be reversed when we exposed the animals to a controllable stress.

Now in terms of transferring that to patients, and this was more interesting to me personally, we had to look at how to manage that stress. The way we are currently doing that is by looking at the effects of exercise, which I presented at the World Congress. The first studies we looked at, which were published last year, were about seeing the impact of exercise in the  animal. We gave the animals access to a running wheel, so it was completely voluntary. So the animals just run and move around as much as they want. When we gave them exercise prior to endometriosis induction, it was able to dramatically reduce lesion size, anxiety, and things like that in the animals, as well as various other inflammatory cells and inflammatory mediators. What obviously translates better for use in patients is to do exercise after the endometriosis has already occurred. That was the work I presented at the World Congress. There we induced endometriosis in animals and then had them exercise for about eight weeks. When we look at the effects, we can see a dramatic reduction in the number of lesions that form, the size of the lesions that form, also some impact on the pain that we observe, and other different symptoms.

Teresa Götz: How can this improve the lives of women with endometriosis in the long term? What could this mean for endometriosis patients?

Prof. C. Appleyard: I think the data we have collected so far suggests that we can use our knowledge of how the disease affects patients through stressors. This gives them the opportunity to take a complementary approach to the usual pharmacological approaches, which often have a lot of side effects or may not be effective. This can help patients better manage their disease and perhaps relieve symptoms. I think that’s one of the most important points. As someone who has a chronic disease myself, but not endometriosis, I think it’s very important to be able to understand your disease and know how to treat it in ways other than just pharmacological medications or things like that.

Teresa Götz: What are your future research goals? Are there any projects planned?

Prof. C. Appleyard: Right now, we are trying to get a better understanding of the fact that exercise works in animals. We are now trying to understand what pathways or mechanisms are behind exercise. Some molecules are involved in that. So, we’re trying to block some of those pathways and then see if that reverses the beneficial effects, and then we’re trying to identify some of the different cells that are involved, the different mediators that may be involved, and how to potentially target those more specifically. I would like to take those findings and apply them to patients and try to find the best treatment modality to recommend to them. Some patients who have severe pain from exercise may not want to ride, run, or do anything like that. But can we incorporate gentler forms of exercise, like yoga. We see that as our main goal for the future. We also have a startup company where we are focusing more on finding non-hormonal therapeutic options pharmacologically. In the future, we hope to combine the two, for example by enriching the environment through exercise or environmental manipulation, which then complements our pharmacological interventions to help patients.

I think there’s a growing awareness that an integrative healthcare team needs to take care of everything. That’s becoming more important, the awareness that the patient can work with different members of the team. Maybe with nutritionists, maybe with physical therapists, with various different members of the team to manage the disease.

Teresa Götz: The patient can choose what she wants to do. Whether she wants to do nutritional therapy or take medication or exercise more. As you said, she is empowered to choose.

Prof. C. Appleyard: It’s a chronic condition. You’re dealing with the stress that results from an impact. I think that’s a big factor in being somewhat in control and being able to manage day-to-day life.

Teresa Götz: What do you think of the digital self-help we offer with the Endo-App?

Prof. C. Appleyard: When I was at the World Congress recently, I was really excited about the session where we were told about all the different digital apps that are on the market right now. It’s a fantastic way to gather information that not only helps patients track and manage the symptoms of endometriosis, but also creates a more detailed log of the day-to-day impact of the disease that can then be shared.

I think it’s a very individual disease, and the more information we can get, the more useful it is. I know I’ve looked at some of the apps and everything else, and I think the added benefit of some of these things that we’ve seen in our own clinical trial with environmental enrichment in patients is that the integration of support groups in different interventions can improve understanding of the disease, and I think all of that is really important in helping patients understand and manage to cope with their disease.

Teresa Götz: Now we reach my last question. Is there anything else you would like to share with those affected?

Prof. C. Appleyard: I have noticed a big difference in the awareness of different groups. Not only in the general population but also among physicians and surgeons. I think it’s important to know that there are many dedicated researchers who are focused on finding new solutions to help those affected. When I was at the World Congress, it was very exciting for me to see how many patient advocacy groups there are. The fact that there are movements in different countries, including Puerto Rico, that are trying to change some of the existing strategies that can help patients manage their daily lives and cope with the symptoms. I think that’s a big positive step forward, and I think that can only get better. I really think that the involvement of different technologies, social media, and patient advocacy groups is very important to drive this forward and hopefully provide more funding for research in the future.

Teresa Götz: I think that’s a very good message for the patients. Thank you for taking the time for this interview, speaking with me.

Teresa Götz