What Rare Disease Patients and Families Need From Clinicians: Philippe Pakter, Rare Disease Parent


“It's a strange odyssey being a rare disease parent. It sort of forces you to question everything about life,” says Philippe Pakter, whose daughter Lysiane was born with Pierre Robin Sequence, a condition that impedes normal breathing and feeding. In this compelling interview with Shiv Gaglani, he shares the wrenching details of his family’s daunting emotional, medical and legal journey. “It's tough, but you just have to keep going and from the hardship can potentially come very beautiful things.” Among the brighter spots of their story are finding a non-surgical treatment that helped with part of Lysiane’s condition, and connecting with a network of dedicated clinicians focused on improving treatments for Pierre Robin Sequence. Don’t miss this opportunity to hear hard won wisdom about ways clinicians can approach their work to be mindful of rare diseases and how they can be a resource for patients and families who are often desperate for answers.  Pakter is a great example of how well-informed rare disease family members are, and why clinicians should listen closely to what they have to say.




Mentioned in this episode: Philippe Pakter's interview with Dr. HyeRan Choo of Stanford University on non-surgical approaches to treating Pierre Robin Sequence https://pierrerobineurope.com/dr-hyeran-choo-non-surgical-orthodontic-airway-plate-treatment-stanford/


Shiv Gaglani: Hi, I'm Shiv Gaglani. As regular listeners know, Osmosis has a special commitment to educating clinicians, patients, and families about rare diseases. In partnership with the National Organization for Rare Disorders, we've worked with dozens of patient advocacy groups and subject matter experts to develop nearly fifty engaging videos on rare disorders that have been viewed millions of times. 


Today on Raise the Line, we're going to broaden our scope and learn about how patients and family members in Europe work with clinicians and others to advocate for themselves and their loved ones. I'm delighted to welcome Philippe Pakter, an international lawyer and legal consultant based in Geneva, Switzerland whose daughter Lysiane was born with a serious form of Pierre Robin Sequence. Philippe is a great example of how well-informed rare disease family members are, and why clinicians should listen closely to what they have to say.


Before we get started, I wanted to thank our CEO at Elsevier, Kumsal Bayazit, who first connected me to Philippe because actually he published his patient experience about Lysiane with some very interesting conclusions that I think are broadly applicable beyond Robin Sequence to the rare disease community in one of the Elsevier journals, Seminars in Fetal & Neonatal Medicine. 


So, Philippe, thanks so much for taking the time to be with us today.


Philippe Pakter: Thank you very much and, you know, because you brought up Kumsal Bayazit, I wanted to really take just a quick moment to express again, my sincere thanks to her because of the fact that she reached out to me personally -- having read the article that I submitted to the journal as a rare disease parent -- and she granted us gold open access. And that's just such a beautiful meaningful gesture. We wanted as many people to read the article as possible, and by giving us open access, for us it was monumental and I thank her again from the bottom of my heart. For the people in my family and in the rare disease patient group that I am with, giving us open access on that journal article meant a whole lot. It really did.


Shiv: Definitely. I will say, you know, now that we're nine months into joining Elsevier...we knew about the values, we knew about the leadership team, but certainly they live it. They walk the walk, they don't just talk the talk. That was just one example, where I told her about our rare disease focus and she immediately said your name, sent me your article, and connected us. So, truly a wonderful leader. I'm privileged to work for her.


So, let's go into your story. I obviously know quite a bit about you and your background. We've spoken a couple of times before. But for our audience, many of whom are current and future clinicians, can you just give us a breakdown of your family story about Lysiane and your journey dealing with the Pierre Robin Sequence? 


Philippe: Sure. Well, first of all, Pierre Robin Sequence was first studied by a French stomatologist, which is like an orthodontist, over 100 years ago, and it really has three diagnostic criteria. A baby is diagnosed with Pierre Robin Sequence if the baby is showing an anatomical defect -- micrognathia -- which is a very small undersized lower chin. The mandible is very small, undersized. 


The second criteria is glossoptosis which is another anatomical defect. The tongue, instead of being in a flat, horizontal position in the mouth, is in a raised vertical position in the back of the throat. And as you can imagine, if you visualize that, that raised vertical tongue is blocking the airway which is creating breathing difficulties, and feeding difficulties. So that's the second thing is glossoptosis. 


And the third diagnostic criteria is actually upper airway obstruction, UAO, as determined by polysomnography, by a sleep study, that the baby is suffering from an apnea-hypopnea index which is above normal for a child of that age. 


Now, what this comes down to in reality is the baby's born and the baby is struggling to breathe.  It's like you're watching your baby suffocating but there's no water anywhere around, but the baby can't breathe because that tongue is just blocking the throat. It's not strictly a mechanical issue. For instance, there are cases where the lower chin is not so small and the tongue is not so vertical, but still, there is breathing difficulty


So it's a complex condition that has neurological components but what it comes down to is that in the vast majority of cases, this seems to be an anatomical problem of the tongue in that raised position blocking the airway and causing the upper airway obstruction. 


Now, another thing is that most of the babies that are born with Pierre Robin Sequence, they suffer from a cleft palate. Not a cleft lip, but a cleft palate, and actually it's an interesting development. It's actually a consequence of the fact that during the prenatal period, the tongue being in that vertical raised position effectively prevents the roof of the mouth from fusing, which it would normally do in the prenatal period. 


So, the important thing to understand for medical students and for clinicians without experience in this rare disease is that we're not looking at a baby with a cleft that happens to have a small chin. We're looking at a baby with a complex rare disease, who happens to have a cleft and may not even have a cleft. Which is to say that expertise in cleft care does not confer expertise in Pierre Robin Sequence because Pierre Robin Sequence is a highly complex rare disease which is still being studied and which experts are trying to better understand. For instance, one of the many things that separates it from a standard case of cleft is that the mortality rate is substantially higher. In one Dutch study, the mortality rate of Robin Sequence babies was eight times higher than babies without Robin Sequence. 


Another striking fact is that when a baby is born and diagnosed with Pierre Robin Sequence, over half of those babies will also suffer from another complex associated condition, and then you start talking about syndromic Robin Sequence. So you don't just have the glossoptosis, micrognathia, and upper airway obstruction, but you have all three of those, plus stickler syndrome or Treacher Collins or some other complex treacherous rare disease which is associated with the Robin Sequence, making treatment that much more difficult and complex. So, it's a really heterogeneous rare disease. It's extremely difficult to generalize from case to case. 


Unfortunately, in many situations what happens to the detriment of the child is that the Pierre Robin Sequence baby will fall under the care of a cleft team, which may be absolutely expert with cleft, but which may not have a whole lot of experience with Robin Sequence. Cleft is common. Pierre Robin Sequence is a rare disease. We're talking about approximately 1 out of 10,000 babies, so it's not a common condition. 


Anyway, our daughter was born with Pierre Robin Sequence and unfortunately in our case it was not prenatally diagnosed although it can be. By simply examining the ultrasound images, it should be possible to identify a radically undersized lower jaw. I remember that my wife, when we looked at the ultrasound images, she said to me, "Philippe, you know it's strange because the baby looks like Bart Simpson." You know, Bart Simpson from The Simpsons has got this very small, recessed chin. And I said to her, "Look, we don't know anything. The experts know what they're doing, and they would tell us if something was wrong." 


But in fact, the experts didn't know and overlooked the micrognathia and also overlooked another warning sign which was polyhydramnios, which was a severe excess of amniotic fluid. So in other words, we've got two big red flags for Robin Sequence. We've got severe micrognathia and we've got a severe excess of amniotic fluid and no flags were raised. Nobody said, "Hey, it looks like we may be dealing with something, maybe we should consider that you give birth in a center of expertise for this rare disease because we don't have a lot of experience with this." No, it was all overlooked, and this kind of underscores the importance of prenatal diagnosis of this rare disease, and I think diagnosis in general of rare diseases. 


Diagnosing rare diseases is not an easy thing and many rare disease patients suffer for many years in what's called the "diagnostic odyssey" where you're just waiting to find out what it is you're suffering from. I'll give you an example. Lysiane was diagnosed with Pierre Robin Sequence when she was born, but she also has an associated condition. There's a genome board that was put together to study her genes and they did identify a certain microdeletion in one of her genes. But, they're not sure if that would explain her many other symptoms, because our daughter has a number of very serious developmental problems which cannot be attributed to Pierre Robin Sequence. 


As I said earlier, Robin Sequence arises in over half of the cases in association with another condition. She's got another condition but they just don't know what it is yet. So we're in this sort of diagnostic odyssey of waiting and hoping to find out what else she has that can explain her other problems. I'm sorry to speak so quickly about so many different things. But, anyway, I hope that I've covered the very beginning.


Shiv: No, you've covered a lot. I was going to reference a couple of things you mentioned, like the importance of prenatal screening because, I heard your talk. You gave  a great talk at the Third Annual Robin Sequence Consensus Meeting back in April. I've seen the ultrasounds of Lysiane and you're right, these things were missed. 


One of the main points you made was that as new parents without any idea of this, you were kind of just trusting in the clinicians who are doing their best -- whether they're cleft expert or a neonatal expert -- but they just miss something or they're not familiar with these rare conditions because as we've shared, when you're in med school the saying is, "When you hear hoofbeats, think horses, not zebras." 


The thing is, there are 7,000 zebras out there. 7,000 rare disorders that affect collectively over 300 million people. And so for those people, they want the diagnostic odyssey to not be four to nine years on average, but as short as possible. As you said, it has real implications. If the condition is caught, you could go to the center of excellence and get the best care. 


You guys in particular have a great story of how quickly you got informed about it and where you've taken that.


Philippe: Yeah, there are very different ways that people respond to the same types of situations, and that's classic in all sort of different aspects of life. When we learned of her rare disease, our way of reacting was we need to learn everything we can possibly learn. We need to just dive in. We're not trained. We don't have a medical background, but we need to do our absolute utmost for our child to understand what is going on, what possibilities exist, and what should the next step be. 


Then there are other parents that are so overwhelmed, so absolutely devastated that they can experience a type of temporary or even long-term paralysis where they just don't know how to handle it emotionally. The way that they react is, they adapt to a passive role of just trusting the physicians to do what they need to do and not to question anything and not even to attempt to get a deeper understanding. It's just too hard. It's too difficult. 


There's no right or wrong in this. It's just a question of your makeup, and we really dove in. We read everything we could.  I have to say that I'm actually American. I was born and raised in New York and so English is my first language and that was a huge advantage because even though our baby was born in France, I wasn't doing research in French. I didn't go to Google French.  I was doing research in English and I successfully located a whole bunch of medical studies which are written always in English because English is the language of international scientific research and that's just the way it is. 


If you're trying to do research in French or in Spanish, other languages, you're not as likely to hit the bullseye. But we found a number of fantastic studies coming from a certain center of excellence in a place we had never heard of before, Tübingen, Germany. Now in Germany, Tübingen is very well-known. It's considered one of the very top universities in Germany. We didn't know about it, but the more we read of the studies put out by their center of excellence in Robin Sequence, the more we were convinced that this really stood apart because it promised to resolve the upper airway obstruction and to facilitate the feeding --and Lysiane suffered from both of those symptoms, upper airway obstruction and feeding difficulties. She was attached to a mechanical breathing machine and a feeding pump which would feed her milk through a nozzle-gastric tube


So, she needed mechanical support for two of her primary life requirements, breathing and feeding. This treatment offered the prospect of addressing those serious symptoms without surgery. It was an orthodontic treatment. A lot of us Americans as kids or our children have had braces, and after the braces are taken out typically the child will receive a retainer, this little thing that they place in their mouth and it just sort of keeps the teeth in the position that they're in, in the correct position. 


The Tübingen Palatal Plate, which is the orthodontic treatment developed at the Tübingen University Hospital, is basically like a retainer which is on the roof of the mouth, but it has this extension in the back. It's an extension which descends almost vertically and in the back of the throat and what that extension does is it pushes the tongue forward and down, instantly liberating the airway. 


So it's like this elegant mechanical engineering solution for an anatomical defect. It may seem pretty straightforward. But in fact, it requires enormous precision to determine the correct length and angle of that vertical extension, and that's typically done with fiber optic endoscopy. A camera is sent into the airway to determine whether or not this prototype of the Tübingen Palatal Plate (TPP), successfully displaces the tongue forward and opens up the airway. It's a question of millimeters. It's got to be perfect, and so it requires a great deal of expertise and a multidisciplinary team. 


It is quite radical because the TPP promises -- and successfully does as demonstrated in 15 years worth of peer-reviewed medical studies -- to resolve the upper airway obstruction and facilitate feeding without surgery. 


Now, there are various treatments for Pierre Robin Sequence. The one that has become quite standard today, particularly in the United States of America is MDO --  Mandibular Distraction Osteogenesis -- and this is quite an aggressive procedure which involves basically fracturing the mandible, the lower jaw, and inserting titanium rods which have screws that the parents, over a course of several weeks, will turn each day or a couple of days to enlarge the gap between the pieces of the mandible and bone will develop to fill the gap. So you're actually enlarging the mandible by creating space between those two points where you've created the surgical brakes. 


Now that involves hardware and that involves at least two rounds of serious surgery. It does seem to be supported by evidence. It does resolve upper airway obstruction. In the best centers, they say that it's over 90% effective but the thing is, the TPP achieves the same goals and it doesn't involve surgery and anesthesia.  I mean, it's quite a remarkable minimally-invasive alternative and this is a fascinating thing because I think that physicians may disagree on the best treatment for any complex condition. There's always room for disagreement. I think that there are certain principles that we can agree to, and one of those is that surgery on a newborn baby should only be performed when it's reasonably necessary. Surgery is a big deal on a newborn baby and not just for the baby, but for the parents as well. It's a type of trauma to send your newborn into aggressive surgery. 


So the third kind of step in this logical progression is that those surgeons that are carrying out MDO on Pierre Robin Sequence patients are, in the vast majority of cases, carrying out unnecessary surgery on a newborn baby, and that's a heavy thing. That's really, I think, a provocative issue that demands exploration. 


Now, one of the things that I do, along with my colleagues in our rare disease patient group for Pierre Robin Sequence babies is we interview leaders in this field and it's a small world. That's true of all of these rare diseases. You've got this small group of clinicians that are really fascinated by that condition and develop deep expertise in that condition, and they generally know one another and they read one another's studies, pre-publication, and provide comments to one another. It's typically this closely knit community from all over the world, you know?


So, I know a good number of those physicians in the clinician community for Robin Sequence and we were interviewing a fantastic, brilliant physician at Stanford named Dr. HyeRan Choo. She is adopting that orthodontic approach to treating babies with Pierre Robin Sequence, and we're doing a really wonderful interview with her that we're going to publish within a week. 


I would love to provide a link if possible that you could include in your notes for the podcast because the treatment has now crossed the ocean and is now adopted by Stanford in America and it's in the process of being adopted at Harvard by another fantastic Pierre Robin Sequence expert named Dr. Cory Resnick. 


Our organization did a wonderful interview with him last year on the prenatal diagnosis of Pierre Robin Sequence because Cory and his team have done really fascinating research on how to use, not just MRI, but also ultrasound to correctly identify with a very small margin of error, Pierre Robin Sequence during the prenatal period.  That prenatal diagnosis comes with many advantages, as we were talking about before. I mean a prenatal diagnosis allows us, the parents, to mentally prepare, emotionally prepare for the tough road ahead, but it also allows us to plan. "Let's give birth in this hospital or in that hospital, definitely not at home," you know? It allows for actual planning. It allows you to begin thinking of the team that you would like to treat your child that has these special needs and so on.


We love when physicians push the envelope, when clinicians challenge established thinking and say, "Why not? Why not try this? This looks promising. Let's pursue it. Let's do some studies, let's really explore this."  Particularly because there is an unfortunate lack of sufficient research in rare diseases across the board, for many complicated reasons. There are just so many thousands of rare diseases. There are very, very complex things in situations like Pierre Robin Sequence. 


There really is a lot of variation from patient to patient, and there are other challenges. For instance, it's tough for a pharma company to dedicate enormous investments into a treatment which really, at the end of the day, may have quite a small market size. You can't argue with financial reality. I mean, it would be great if public resources were devoted to research into rare diseases. But the fact is that we do face these sorts of limitations that result in the fact that the vast majority of rare diseases have no approved treatment or cure. 


That's one of the devastating realities all of us rare disease patients and parents have to live with every day: 90% to 95% of rare diseases have no effective treatment or cure. So, we are living day to day, week to week, month to month in the hope that there might be some light at the end of a long tunnel. But it's really a tough situation to be in. It's really tough. 


That's why it's so beautiful when we see support from the private sector, a beautiful gesture being the one that your CEO at Elsevier provided open access for our article because we think that the article that we wrote will help open minds of clinicians that are involved in Pierre Robin Sequence, as well as students and clinicians that are still in a training period. We raised a lot of interesting questions. Please read the article, because the article is not some emotional tearjerker -- here's what happened to us, here's our painful patient journey. It's much more than that. 


We talk about the various treatments from the perspective of the patient. And that's important because you've got data, but you also have people, and both are kind of key in the mix. So, please read the article whether or not you know much about Pierre Robin Sequence because I think that it will help you to see things from a kind of slightly different angle, and that's always helpful in life.


Shiv: Absolutely, and I'm glad you touched upon that. There's so many threads we can pull on based on what you were just saying. I did read the article and one of the things I love about meeting people like you in the rare disease community, in general, is just how clearly passionate you are about it because it's your daughter. It's your family.  On this theme of partnering with patients and clinicians, think about what would happen if patients or family members with the more common diseases -- like diabetes and hypertension --  took 0.01% of the motivation and passion that's evident in so many of the rare disease community groups. We would be able to prevent so much needless suffering and pain, and healthcare costs. 


One thing I want to touch upon which you made clear in your talk is there isn't going to be a center of excellence for every rare disease in every country. You make this point in your article that it's important for governments and others to make it even more possible...not to hinder, but to help rare disease patients to get together and go to these centers of excellence for the best care. So, for instance, they're not going to a cleft specialist, but they're going to a TPP specialist, whether that's at Stanford or in Tübingen. 


Can you talk a bit about some of the challenges you faced? Lysiane was born in France, the treatment's in Germany. I think with your legal background, you're involved in getting the EU to pay for the significant health care costs you and your family are facing. 


Philippe: Well, I do have quite a bit of experience in the question of cross-border healthcare in Europe, which is a funny thing because I'm American. I'm really very American, but I learned a lot about cross-border care in Europe, particularly in the context of rare disease patients because of the situation we had with our daughter Lysiane. 


She was born in a center which was not a center of excellence for her rare disease. She has a syndromic form of Pierre Robin Sequence. She had and continues to have very serious problems. She should have been permitted to transfer to a center of expertise and we had correctly, independently identified the center of our choosing, which was in Tübingen, Germany. 


And you might think, "Well, you're in France and now you're talking about going to Germany," but Germany is just across the border. It's not even a very long drive in an ambulance. You're there, it's a transfer.  So I did the research and the most important law in question here is called Regulation 883 that says a patient in the European Union who has a rare disease has the right to access a rare disease treatment in another European Union country if that treatment is not available where they live. 


So, we applied for authorization for our daughter to receive the TPP treatment just across the border in Germany. We did a really beautiful application. I included literally six medical studies. We have a controlled study dating back to 2007 and a series of studies after that which looked at this treatment from every angle -- and always evidence-based medicine -- pre and post-intervention PSG, the polysomnography, and weight gain data. So this is not just a bunch of clinicians saying, "We consider that this treatment is effective." This is objective criteria and it was really high-quality studies put out by the Tübingen University Hospital Centre of Expertise. 


Well, the application was rejected and so what we faced was an indefinite period in the ICU. Our daughter had already spent five full weeks in the ICU connected to a mechanical breathing machine and a feeding machine. Anywhere in the world, five weeks in the ICU is going to cost a fortune. So we were actually asking the French Administration, "Let us save you money. Let us get our daughter into a treatment which promises to liberate her from the breathing machine and get her out of the ICU in two to three weeks." That's it, you know? And they said no. So this wasn't a situation where the rejection was based on the exorbitant cost of some gene therapy or the questionable efficacy or safety, it wasn't that at all.


Let's just put it this way. The rejection was not based on medical reasons. So we were now looking at keeping her in the ICU another five weeks, another ten weeks. There was no scheduled date of release. The ICU had become our second home, I mean, literally, we would go there, put our stuff in the lockers, wash our hands and arms, and wear the gowns and spend the whole day and evening. We would have to leave at night. Go home again, you know the cycle. It was devastating. It was very, very painful. 


We decided on getting a bank loan. My father actually borrowed money against his home in New York and he transferred the money to the German hospital and we transferred Lysiane to Germany. We decided the top priority is getting her into the treatment because it's time-sensitive. The earlier the treatment begins, the better, and the more favorably the babies respond. We thought that the legal and administrative disputes should be secondary in importance. 


Well, she got the treatment as promised. She was liberated from the breathing machine. We were out of the hospital in I think it was 19 days and it changed our lives. Remember, she had never left the hospital. She was born in the hospital, never left five straight weeks in ICU with no hope of getting out in another five weeks. We didn't have any idea. And so we were very pleased with the results and then we took up the administrative appeal and that is a kind of incredible thing because it's continuing today, and this dates back to 2017. 


We decided to sue France in 2019 for violating EU law. We knew we had the right to access the treatment. The European Commission specifically looked into the case and decided that France was in violation. Well, we're in August 2022, so we have waited three years and six months and we have not had a single case hearing. and now what you're looking at is not just France having violated EU Cross-Border Health Care Law. But now France is in clear violation of basic human rights because it is a basic human right that every person has the right to a fair trial within a reasonable time by an independent and impartial tribunal. In America, we think of this as due process. But the point is you can't make somebody wait three and a half years before giving them a day in court, but that's what France has done with us. But we're not going to give up. We don't care if we've got to fight for five years, ten years, fifteen years. We're going to get vindicated. 


Now, what this really all points to is that when a rare disease treatment is available -- in the relatively unlikely scenario where there is a safe and effective rare disease treatment available -- patients should be facilitated in accessing that treatment. People, administrators, healthcare systems, should be bending over backwards to do whatever they can do to get that rare disease treatment to the patient as quickly as reasonably possible.


When a safe and effective rare disease treatment is available, please for God's sake, help the patient get the treatment. Help the patient by all means. I mean, it's just such common sense. It's just about basic human decency. Why put-up obstacles? Why create difficult nightmarish situations like the ones that my own family is facing. But I don't want to try to evoke pity. We believe the hardship that we're enduring in seeking justice helps to shed light on a problem that many rare disease patients face, and that is access to care. 


I would like to make a request, a sincere and heartfelt request, to the students and young clinicians that are listening to this podcast. If you face a patient with a complex rare disease, it is very likely that you are not the best-qualified clinician to treat that particular patient. Your job is not to fake it till you make it. It's not to say, "I've got this." Put your confidence to the side and just accept the fact that there is probably a clinician somewhere out there that has spent years and years and years studying this particular rare disease, who knows it better than anyone else, or there's a small network of people like that clinician.


Your job as a young clinician or student is to be a resource locator. You go and read the studies on that rare disease. Look at the authors whose names are popping up again and again in the literature. Reach out to those people and say, "Look, you appear to be a real expert on this condition and I'm dealing with a patient who we believe is suffering from this condition. We'd greatly appreciate your involvement, your ideas, your suggestions as to a care pathway. What do you say?" They'll write back to you because those clinicians have the passion for that rare disease and the patients affected by that rare disease. 


So please, young clinicians, find those experts that are out there and make the connection and help to serve as the bridge between the rare disease patient that's in front of you and that expert that is an email away. They might be in a different state. They might even be in a different country, but it's very likely that based on their passion and their fascination with this rare disease, they will do more than you imagine to help you and to help your patient. 


Please think of that. I beg you to think of that. 


Shiv: That's incredible advice. You put me in touch with Durhane Wong-Rieger at the Canadian Organization for Rare Disorders and we had a chat yesterday. She'll be on the podcast in a couple of weeks. She mentioned a similar thing and suggested we make a course that basically helps our audience and early stage healthcare professionals not only identify these rare disorders better, but do a double-take on it and hopefully with better AI --  reading of these ultrasounds and things like that -- it won't be up to them to know every rare disorder. 


Being that bridge and resource is not really taught. There are rare disease communities that are lucky to have advocates like you who are extremely intelligent, extremely motivated. If anyone listening to this podcast missed the intro about who you are and what your background is, at different points they would think, "Oh, this is a physician based on how easily he talks about all these different conditions; this is a parent when you talk about your personal journey; this is a lawyer talking about Cross-Border Health Care Law; this is an advocate leading an organization doing rare disease work. 


That's an important point too. You find the right combination of a highly motivated individual or group of individuals and you build the care team together. The people who are listening to this most likely are never going to see certain conditions. But the fact is if they listen to this, or if they watched an Osmosis video on this topic then somewhere in the back of their head, they know that there's some things they don't understand and have that humility that they don't understand it.  And they will think about then being that bridge and advocating for their patient or having the nurse team do it, having a social worker get trained up on how to do this. It's really critical. I'm glad you mentioned that.


I did want to go into two other questions and leave it open-ended. You've already given a lot of advice to our audience, but zooming out, what other advice would you want anybody listening to this to know about, especially when it comes to rare disease?


Philippe: I would like to encourage listeners to seriously consider exploring a rare disease and diving in and immersing yourself into it. These are really complex conditions and as students and young clinicians, you are all people with way above average IQs and it might be a really beautiful match. You're really smart. You're really ambitious. You've got this medical background and here's this profound mystery of a rare disease and you could be one of those global experts on that rare disease. You might find that the deeper you go and the more you learn, the more you are loving this exploratory mission. 


It can be really fascinating. It can be daunting, it can be discouraging because so many of these conditions don't yet have effective treatments and you will see patients come and unfortunately, go. The mortality rate of these rare diseases is just unspeakably high and concentrated among very young patients. But that makes it more meaningful because this is where the battle is being fought. I mean, one of the most overlooked areas of healthcare is rare diseases. 


Like you have said, Shiv, there are thousands of rare diseases. Most of them have no effective treatment or cure and with what we're learning about genetics, things could be changing. We could be turning the corner now with gene therapy and so you could be the one that makes a huge difference. Maybe not for the whole world, you know? Not like Jonas Salk. But for a small population of patients that desperately need help and that would just be absolutely devoted to you for your efforts for the very fact that you're spending your time and your brain and your energy into trying to make a difference for them. 


You cannot underestimate, you cannot imagine the real loyalty and devotion that we rare disease patients have for those hardcore clinicians that are at the conferences for our rare disease, that are publishing the papers about our rare disease. We look at them as the shining hope for the future of our children and I would really encourage you to consider the rare disease space. 


It's just an idea. The world is open for you. You can go in so many different directions, but think about this one, think about the rare disease path. It's a worthy, worthy path. 


Shiv: I think that's beautifully articulated. It's a story that keeps coming up...one or more clinicians who dedicate their life to a rare disease whether because it's intellectually challenging or they have personal stories related to this condition or they are just kind of curious about it or want to throw a life raft out for this community that needs a lot of help. 


I will say too, though, as far as the Salk comparison, there are examples of rare diseases that when the clinicians or researchers spent the time uncovering why they happen there are far reaching consequences. For instance, familial hypercholesterolemia. The research behind that rare condition led to the development of statins, which now over 200 million people take around the world. So it's very possible that some of these very daunting and challenging conditions...underneath all those layers there could be could some foundational physiology or pathophysiology that could be used for many other conditions. 


So, I would make that clear to our audience and hopefully, we can get some of them motivated to pursue this path. Two other questions. How is Lysiane doing now? She's five years old at this point, I think?


Philippe: Yeah. She's five years old and she's a handicapped child. And yeah that's a strange thing. There's this overlap between the rare disease community and handicapped or "people living in a situation of handicapped" as they say in Europe. She's both.  She's got a rare disease -- one that's been diagnosed, and one that they're still trying to diagnose -- and she's handicapped and it's quite challenging. It's very, very challenging. 


We do our best every day and we have found that you learn a whole lot about yourself as a person, as a parent. You are pushed in ways where you're being forced beyond what you thought were your limits. And it doesn't really get easier. Honestly, it doesn't really get easier. Things change but it's a strange odyssey being a rare disease parent for us, and I think for many rare disease parents, where it just sort of forces you to question everything and ask big questions about life.


You cannot keep asking "why us?" You have to kind of shift gears into what's next. You know, what's the next step. You don't have that luxury of indulging in self-pity. You've got to meet the challenges of each day. When you're a rare disease parent, you do everything you can for your child to the very best of your abilities. 


One of the things that we worry about -- and I know that a lot of people in our situation will understand exactly what I mean -- you worry about what will happen when you're not around and how your child will be cared for and in what way. That's one of those sort of weird things that the typical parent doesn't really face.  You're hoping your kid gets into an Ivy League college and gets the job that he or she wants, has a happy marriage. We actually worry what's going to happen when we're dead. That seems really morbid, but that's kind of the intense gravity of the rare disease experience, particularly when the rare disease has a neurological component...not just physical, but intellectually handicapped. 


I mean, it's tough. It's tough. But you just have to keep going and I think that from the hardship can potentially come very beautiful things. I really want to emphasize that over there in America, I know that NORD -- which has just been such an incredible game changer in the landscape for rare disease patients in America -- it was started by a woman, Abby Myers.  She described herself -- and this is a quote -- she said that, "She's a simple housewife from Connecticut with children who have a rare genetic disorder." Well, that simple housewife created NORD which is responsible for the passage of the Orphan Drug Act of 1983, and no policy in the world -- not anywhere in America or Europe -- comes close to the benefits that have been produced by the Orphan Drug Act of 1983. 


So the point is that parents without medical training who have skin in the game -- children with a rare disease or they themselves suffer from a rare disease -- they can do good things. They can be meaningful parts of the movement. It's really about the clinicians, but those that are not clinicians can also contribute in a very meaningful way and open doors for the clinicians. Help to get research funding and help to push through legislation that creates incentives for Pharma to invest in R&D and so on. 


And it's like you said, you know, R&D in rare disease orphan drug development often has unintended beneficial effects for the general population. When you study extreme conditions, you often learn about more common conditions. So don't look at it as "it's just charity" for tiny sub-patient groups. No. It's science, and through this research you can learn and you can make a difference for many, many, many people, not just those rare disease patients. 


Shiv: Absolutely. That's such a beautifully stated example of this famous quote, "Don't doubt that a small group of highly motivated people can change the world. Indeed, it's the only thing that has".


Philippe: Margaret Mead, right?


Shiv: Margaret Mead. Yeah, exactly. I paraphrased it, took a lot of liberties in that. But yeah it's one of these quotes that's very motivating. So, whatever we can do to help raise awareness and education is something I know we're committed to at Osmosis and Elsevier. 


Philippe, is there anything else? We've covered a lot of ground. I'm deeply appreciative of your time. Anything else you'd like to leave our audience with today before we let you go? 


Philippe: I'd like to say that sometimes physicians can feel like they're on the hot seat. But I want to say as well that you clinicians have one of the toughest damn jobs out there, okay? The stakes could not be higher and there is so much that we don't know. We know a lot but there's so much that we don't know. And so I want to thank you for doing one of the hardest damn jobs that anybody can do and we appreciate you and we need you. So, keep working and keep your faith and please accept my thanks and admiration for your hard studies and your hard work and the stress that you face every single day in your career as clinicians. Thank you very much. I appreciate it and my whole family appreciates it. We do need you, and we thank you.


Shiv: Philippe, thank you so much for taking the time to share your story and so many insights. It's going to be very hard for us to choose what the quote is that goes with this podcast. And I'll say that we've done over 300 podcasts...I've probably done about 70% of them as the host. This is definitely one of my favorites, if not top favorite just because I hear the passion. It has a lot of great takeaways and I really want all of our listeners to engage in the ways you said. Whether it's being that bridge when they see something they don't understand or going all the way and becoming a real advocate or a leader...attending the symposia for a specific condition and maybe having an incredible impact from a policy perspective or research perspective, a clinical perspective. Whatever they can do. 


I truly, truly appreciate your time. I'm so glad Kumsal connected us. 


Philippe: Thank you. Thank you, Shiv. Thank you, Osmosis and Elsevier. I really appreciate you taking an interest. I really appreciate it. Thanks a lot for this opportunity. 


Shiv: Well, our listeners can expect multiple more episodes featuring rare diseases. It's a space we're very passionate about for the reasons we just spent the last hour discussing. With that, let me say thanks for checking out today's show, and remember to do your part to raise the line and flatten the curve.