OM DENNE EPISODE
One Dad's Mission to Cure His Son's Genetic Disease
When Anton Morkin's son was diagnosed with "idiopathic" pulmonary hypertension, he refused to accept "no known cause" as an answer. What followed was a crash course in genetics, the discovery of a rare mutation, and the formation of a worldwide coalition, TBX4Life. My name is Anton Morkin. I am from Germany. In 2020, my son was diagnosed with severe pulmonary hypertension. We were just rushed into many new things for us. People were saying your child will die probably in the next week or month. They did not know how long he'd survive. They told us this is pulmonary hypertension. That was the first time when I heard about it. I have a degree in physics and I work at Apple as a IT professional. My education in biology and medicine is zero. I didn't know anything about these type of diseases. I didn't know really that there are so many diseases which do not have any cure. My biggest worry was about cancer. We were just rushed into this within a few days. We were told that my son Daniel, he'll not recover, most likely, from this severe pulmonary hypertension and he's not reactive to what they called NO (nitric oxide) test. They started to talk with us about lung transplantation. All of that happened just in few days. My story here may be very similar to stories of many, many families. Still, Daniel surprised everyone. Apparently, he became actually very responsive on the therapy. Within just a few weeks, he started to recover very well, which surprised us and also his doctors, because they didn't expect that. That gave us some time to reflect. I was doing the following things… Every day I was caring for my son. He was 16 months at that point, so I was caring for him on the day, because my wife was caring for him in the night because he was in the ICU. During nights I was studying pulmonary hypertension to understand what is this and what I can do. So, I started to reach out to other people and exploring what is possible, how to treat it better. That was my first thing. Still, I was not satisfied with the fact that I do not understand why that happened, because the first diagnosis was idiopathic pulmonary hypertension. There is not any explanation actually why that happened. For me, that was always disappointing, because it means that if you don't know why that happened, you don't know how to treat it. Then, where Daniel was diagnosed, they ordered a genetic test, which was really nice, because I know it doesn't happen in every place. Apparently, there are places where we still do not refer to genetic tests, which is, in my opinion, really weird. Because certainly genetics play in children more than 50% by genetics from this pulmonary arterial hypertension. They performed a genetic test. It took a while actually for them to get a result. It took months. But they did that and they did find a mutation and a gene, which is named TBX4. That was the first time when I heard about TBX4. That forced me, actually, to go into that area. First of all, that gave me at least some sense. Okay, so something got broken in his DNA and that is the reason. At least I know where to look to. I started to research in genetics. I had to educate myself on genetics actually. I educated myself on pulmonary hypertension in pulmonology, then in genetics. After that education on genetics, I started to understand how the things are connected together. TBX4 syndrome, it affects lower limbs, it then affects lungs during embryo development the most. Depending on the mutation and that a combination of unknown factors, it can create a different impact on the body. On a skeletal side, it primarily affects a knees, that is so-called small patella syndrome. It is also rare disease. I was living with a small patella syndrome for 45 years without knowing that. When I had some troubles with the knees, I came to an orthopedist and one of them said, "Your knees are so strange, I never seen them. Never seen such." Okay, okay. So how does help? Finally, with this TBX4 syndrome, I was able to explain this. Small patella syndrome literally means that your patella is small and sometimes it's positioned higher than it should be. If you don't train your knees in the right way, then you just have increased pain. This is what happened with me. So it happened from 25 till 35. And then at 35, I was barely able to walk on the stairs. That is just because of this gene mutation. Or hip replacement, that's another one. In adults for example, hip problems can also be severe. If in the family there are such histories and there is one with pulmonary hypertension, then I would rather go and do a test, because it's very likely that it is TBX4. In some humans, it can create more damage. In some humans it creates less damage. The good example of that is me. I carry the same gene and my son actually inherited this gene from me, this broken gene from me. I'm almost 50 years old and I'm still alive. They named me an asymptomatic carrier. I hope that I will continue to be an asymptomatic carrier. Who knows? But I didn't get pulmonary hypertension. But at the point, it was important for me was to understand that, okay, so this is not idiopathic, this is good. I do know what is my enemy and what I can fight with. I started to separate this story from the story of general pulmonary hypertension. Because when you look at pediatric pulmonary hypertension, diversity is so high and you do not understand what to expect, because there are children dying. As long as there are no differentiating factors, you do not understand what to expect. So, in the first year when we were diagnosed and we gotten to those Facebook groups, a lot of children are diagnosed with a very severe situation, but then it can go to a more stabilized scenario. That is actually what happened with my son. He's now six years old. He's stable for the last five years. He's on triple therapy. He's living a full life. He's doing everything, everything. He does Taekwondo. He does swimming. He's capable of doing the things. Having him in that condition allows me also to do more things. I do understand those parents also who for example, have babies in ICU, right? As long as you stay there, you do not have that much chance to do some other things. I started to connect families. I was able to identify them actually, because since this is a skeletal disease plus lung disease. Skeletal signs, you can see them. Interestingly, some of the families, they actually found that they maybe have the TBX4 for mutation by skeletal signs. That is why from the age of 25 years old, I was not able to run and jump. The gene affected my knees. They connected those things and then we made an official test and that confirmed also that I have that mutation. Since I was able to connect several families, I thought, "Okay, so maybe we can somehow do this together." We can help each other. Help to bring this disease to be more heard, to make some noise around this disease. Fortunately, this knowledge was already there. The correlation between TBX4 and pulmonary hypertension was made only in 2013. Before that, nobody knew about that. The correlation between TBX4 and developmental lung disease was even later in 2019, and my son was diagnosed in 2020. I started to read those papers about this TBX4 and how that works and how that creates pulmonary hypertension. I found that in those publications, they say more research is needed, more research is needed. That data isn't complete. They just described few cases. Few cases in France, few cases in the US. In my career, I've been a program manager for 20 years. Essentially, what I've been doing for 20 years is connecting people from remote places, connecting them to deliver something. I'm thought maybe I can do something here. I approached just a single person. I was so lucky that I approached the right person. I approached Dr. Eric Austin from Vanderbilt University. He was so great in the conversation. I just approached him, just made a Zoom call. We had a conversation and Eric said, "Maybe I can help somehow or you can help somehow." Eric didn't know what to do and I didn't know what to do, but we had a great call. So he said that, "Yes, I will support you as long as you know what to do." I was lucky to attend soon a seminar for people who would like to start a rare disease research organization. This helped me a lot to understand next steps. Then, I approached Eric and said, "Okay, I know what to do. Let's start a foundation. Let's start this international collaboration." That is how we actually create the TBX4Life. It took us about maybe one year to ramp it up to understand how to engage professionals, how to position this foundation. When I was starting this, there were already enough different foundations, especially for pulmonary hypertension like phaware, for example. There's phaware, and PHA US, PHA Europe. I was thinking, okay, so I do not want to create another pulmonary hypertension organization. It does not make any sense. What I wanted was to bring the focus on my case and that focus on TBX4. I wanted to be sure that my specific cause is on top. I'm a person who can reach out to anybody to make this happen. We cover holistically the genetic condition and focus on that. On the community side, I started to connect more and more and more and more people. Currently, we are still relatively small, but again, we are talking about ultra-rare disease. I think that it's good that we already have more than a hundred members in this community from New Zealand to Europe, Australia, almost every state in the US, in Spain, Germany, Netherlands. About 15 countries, currently, whom we connected. We connect them together. We educate them as much as possible, give them information about this disease, connect them to specialists where that is possible. But we also give them a platform also to exchange that information between themselves. Because yeah, they can join for example, and they should join those communities for pulmonary hypertension, but those communities will not tell them about the experience that we have for this specific disease. We give that portion which is more for them. A couple years ago, we achieved a state where we were comfortable to set a goal for the organization to cure TBX4. We all want to do many beautiful things, but essentially I think that for our children we need a cure. For me, that was extremely important. In the beginning, we were very cautious of not setting some artificial goals. Because I'm not a scientist — I can say anything. I can say any nonsense. I can say, "Okay, let's cure it tomorrow." But clinicians and scientists — they cannot do that, because they do understand how much is behind that. I understand that well. It's not an easy journey. It's a very, very tough journey. It can be multi-year or can be even multi-decades, but important as long as there is such a goal and people are committed to that, then that drives us. What was so essential for me in "what would be the roadmap to cure?" Essentially, this is like a drug development lifecycle. We need some understanding on the genes. We need understanding on how genes work, proteins work, how the cells and lung development happens, and we need to find medical compounds and try them. For example, first in the very basic models. You know what is possible currently? You can take blood from a patient and from the blood you can create cells and those cells are reprogrammed. There are ways to reprogram them into the embryonic state. You can just take blood, reprogram it to that embryonic state (so-called induced pluripotent stem cells (iPSCs). Then, from that state, program them to your lungs. You can create just a cell which is for lungs. They are capable, even now, to create so-called organoids, which contain different cells. Because for example, in the lungs there are about 10 different types of cells, and they co-culture them together and create organoids like a small part of the lung. There are efforts, by the way, now, in science to grow the whole lung, because there is a big, big problem, for example, for lung transplantation that you transplant the lungs, but those have a lot of troubles, because the body thinks that there's something wrong. There's acute rejection, chronic rejection. All of this stuff happens. So, if someone would be able to grow lungs from the stem cells of the patient, then there'll be none of those problems. The science is moving, so that's why I'm so fascinated now with all this happening and why actually this 'cure TBX4', for me, is like, yes, maybe this is very ambitious, but still it's not necessarily unrealistic, because science currently is going amazingly fast. Just amazingly fast. It is just exponential. What was taking 10 years five years ago, now can be done just two years. One of the things, for example, which we're now doing in this initiative, we are collect blood from patients and we would like to enroll more and more patients so that we can create those stem cells and make those models so that we can test different medical compounds and see if they can actually recover this impact. If that will be found in stem cells, we can do that on animal models like in mice, for example. When we can prove that in mice, then we can go and try that on humans. It's very simplified picture, honestly speaking, but I know the path. We have in our initiative, all the people who do understand this in all the details. We have researchers for cells, people who research for animal models, people who are geneticists, people who research how genes are connected. We have people who use artificial intelligence to study correlations between genes. We have clinicians, and more. I visited almost every pediatric pulmonary hypertension center. I was in Colorado, in Boston, in many other places. I met with almost each of those who lead pulmonary hypertension programs in different sites. In Texas, in Vanderbilt, at UCSF, and Stanford, and also in Europe and Netherlands. We connected all these clinicians together. I think that we have great number of very motivated and skilled people. We just need a little bit of push and continue that. I keep a photo of my son just in front of me on the phone. A photo when he was first diagnosed. It's emotional. It's five years ago and it's still emotional. I think that this initiative, it's also my response. I'm not sure if I will really make something for him. I don't know. But I know that if I did not do that, there is no excuse. I went through that journey of five years. I keep it separate. I separate his story and this story for TBX4Life, my son's story and story for TBX4Life. This is intentional, because I cannot put 100% of my time and just say, "Sorry son. I cannot do anything with you because I'll be doing things for TBX4Life." I think that it's unfair to him. So, my biggest challenge is actually to keep that balance, have enough time to be spent with him and with the rest of my family. I have another daughter who is, fortunately, not affected. She's not a carrier. I have a primary job to come to. All of TBX4Life is just truly volunteering. I do not get a penny for TBX4Life, as well as others, who joining me to volunteer their time. We are not paid. We have our other jobs. I have my job, which brings me that income, which allows me to live that life, which I can , and I need to balance it. My job, family and TBX4Life in the right balance. This is not that easy, but that is possible. I do what is possible to increase his chances. That's the thing, right? Of course, I will be very happy to save as many children as possible, but I cannot just put my whole life into it, and my son can't live without me, right? What I want to say and share actually maybe in this podcast as well, is those who start something, doing something, create initiatives or support initiatives, who devote their time to make to mull out, etc. That deserves it. That must be happening. This era of rare diseases and advocacy groups for rare diseases started to transform maybe about 15 years ago. This is more and more respected. That also part of my motivation, because I don't know if it would be less positive for me if I was just spending every day seeing how my son… He's fortunately stable, like I said. But I don't know how long he'll be stable. I don't know. I just can't sit and do nothing, I just cannot do that. I'm not religious, so I cannot pray. Well, I can, but it's unlikely to help. So, I cannot outsource this to anybody. So, I'll do that myself. I need to do that myself. If it'll help, it'll help. If it will not, I at least I tried. My name is Anton Morkin and I'm aware that my son is rare. Learn more about pulmonary hypertension trials at www.phaware.global/clinicaltrials. Follow us on social @phaware Engage for a cure: www.phaware.global/donate #phaware Share your story: info@phaware.global Like, Subscribe and Follow us: www.phawarepodcast.com. @TBX4_Life
