Building Awareness and Communities Around Rare Disorders – Dr. Edward Neilan and Rebecca Aune of NORD


In medical school, when taught about differential diagnoses, students are often taught, "if you hear hoofbeats, think horses, not zebras” says Rebecca Aune, the Director of Education Programs at National Organization for Rare Disorders (NORD). NORD, she says, represents twenty-five million American zebras living with rare diseases every day, many of whom undergo a deeply frustrating and isolating odyssey as they seek an accurate diagnosis. The reasons for this are numerous, Dr. Edward Neilan, the organization’s Chief Medical and Scientific Officer, tells host Michael Carrese. But NORD is working to address many of these problems at once -- at the level of the patient, the doctor, the research, and the medical system as a whole. Tune in to hear how a 1980s law dramatically increased research into rare disorders, how the human genome project has revolutionized their treatment, and what a future of better diagnostics could look like.




Michael Carrese: Hi, everybody, I'm Michael Carrese. For the twenty-five million Americans with rare diseases, and their loved ones, the journey to diagnosis and treatment can often be long, complex, and frustrating. That's where our guests today enter the picture. Dr. Edward Neilan is Chief Medical and Scientific Officer and Rebecca Aune is Director of Education Programs at the National Organization for Rare Disorders.


For nearly forty years now, NORD has been an indispensable resource for patients and families, medical professionals, and those seeking to develop new diagnostics and treatments. It also supports the work of three hundred affiliated patient organizations.


Osmosis has had the privilege of collaborating with NORD on nearly twenty videos, which have been very positively received by health professionals and the people in their care. We're really pleased to welcome both of you folks to the show, and we're looking forward to spending some time today helping our audience understand more about NORD and the very important work you do. Thanks for coming.


Dr. Edward Neilan:Thank you.


Rebecca Aune: Thanks for having us.


Michael Carrese: I'd like to start first with some career highlights, and to learn what drew you to the field of rare diseases and to NORD, particularly. Dr. Neilan, do you want to start?


Dr. Edward Neilan: Sure. I'm a pediatrician and a medical geneticist, and I really got started on this pathway when I was an undergraduate studying Biology. I got fascinated by genetics, particularly the great puzzle of how the relatively limited amount of information in our DNA, which is about 1 GB of information, somehow provides all the instructions for our biochemistry and our embryonic development, and some of our functioning. To me, that's an amazing puzzle. There is less than one bit of information in our DNA for each cell in our body.


Michael Carrese: Yeah, that is pretty amazing.


Dr. Edward Neilan: I was also interested in applying that to help patients, ultimately. After college, I decided to enter a federally-funded MD-PhD training program, which I did at Stanford University. There I worked in experimental mouse genetics. Learning to alter the mouse genome on purpose to see what effects that would have. I was drawn towards working with children in the clinic. It was just, for me, fun when they were healthy, and impactful when they were ill. That was a natural pairing with genetics, since many genetic diseases manifest themselves in childhood.


After finishing medical school, I decided I would pursue residencies in both Pediatrics and Genetics. I did that at Boston Children's Hospital and Harvard Medical School. After that, I opened a research lab at Boston Children's Hospital and joined the Harvard Medical School Faculty from 2004 to 2016. I was full-time there. I still retain a part-time appointment there, but after serving a term as President of the Medical Staff at the hospital, I decided to try something else. I worked for four and a half years in the pharmaceutical industry, again, supporting rare diseases.


In 2021, just over a year ago, I was offered a chance to join NORD, which I looked upon very favorably as it represented a return to working purely for the patients. I also had a soft spot for NORD, since back when I started my own research laboratory. NORD was one of the first—in fact, the second—organization to give me a research grant to help me get started.


Michael Carrese: You never forgot. That's great. That all fits together nicely. Rebecca, what about your story?


Rebecca Aune: I landed at NORD from a non-scientific route. My career to date has been entirely within the nonprofit sector, and began while I was earning my Masters in Public Administration. I fell into rare diseases in my work with Starlight Children's Foundation, where I helped thousands of pediatric patients and families living with serious chronic and often rare diseases. I then worked for the Pulmonary Hypertension Association, which is actually a longtime member of NORD's membership network.


There, I directed PHA's Continuing Medical Education Programs, which had in-person and online components, and I oversaw PHA's Patient and Caregiver Education Portfolios. Some of the work I was most proud of was revamping PHA's online educational programming with professional videography and animatography and improving the learner experience, and therefore increasing CME course completion. I came to NORD in late 2020, and I lead the Educational Initiatives Departments. We work to grow NORD's educational content and programs for patients and caregivers, health care professionals, and students.


Michael Carrese: Even just in the first few minutes, I think people are getting a sense of the footprint, that NORD touches so many different organizations and professionals. Very well-regarded, of course, in the medical community, but for listeners who might not know as much about it, Dr. Neilan, can you just add a bit to what I said at the beginning and what you folks have said so far?


Dr. Edward Neilan: Sure. I think it's important to know a little bit about the origin story of NORD, which is tied in with the Orphan Drug Act, which was signed in 1983 after a great deal of advocacy by key founders of NORD. That Orphan Drug Act has provided incentives to industry that didn't exist before and has really driven a revolution in the development of drugs for rare diseases. There are many, many times more drugs for rare diseases now than were developed before 1983. In fact, in the last few years, the majority of drugs approved by the FDA have been for rare diseases.


The founders of NORD didn't want to end their efforts or potentially fall apart after that, so they formed NORD a few months after the passage of the Orphan Drug Act. NORD's Policy Team is still active in Washington, DC, defending the Orphan Drug Act, keeping it intact, and advancing other legislative and policy agendas, but we also now have important initiatives in research, education, and patient care.


Michael Carrese: Rebecca, on the education front, picking up on that, give us an overview of that effort, and particularly, how much do you direct your educational outreach toward providers versus patients and families?


Rebecca Aune: Sure. When I talk about the education strategy at NORD, I often describe it as a straddle strategy because we are dedicated to educating patients and caregivers, and the healthcare professionals who treat them simultaneously. Our main patient and caregiver education event is the Living Rare, Living Stronger Patient and Family Forum, held annually in a different city each year.


This is a virtual conference centered on living your best rare life. It offers education and wellness sessions, networking opportunities, and sometimes entertainment for people living with a rare disease and their families. It's really a one-stop shop to get information on how to find your people in the rare community; how to fight back or fight forward through advocacy; how to manage your health and cope with rare diseases; how to participate in research, you name it.


Really this is often the first opportunity that people living with rare diseases are in a room with other people who just get it. We also offer online educational opportunities such as our video library on rarediseases.org, which is targeted for patients and caregivers. This is a joint project often with our partners at Osmosis, where we deliver videos on specific rare diseases, which complement our rare disease reports, which are part of our rare disease database online. Eighty-four percent of NORD's website's traffic comes in through our rare disease database. When patients and families are doing exactly what their doctors tell them not to, and the first thing we all would do, which is Google the diagnosis.


Michael Carrese: Right. Yeah, that's a double-edged sword, for sure.


Rebecca Aune: Since late 2019 to early this year, our continuing medical education program, which is produced in partnership with PlatformQ Health has educated more than eighteen thousand healthcare professionals. While reach is very important to an organization trying to raise awareness about the importance of screening for rare diseases—and early accurate diagnosis—along with the breadth of the program, we are also focusing on the depth of the program, meaning, what are the outcomes? Our participant evaluations continuously show positive changes in both knowledge and clinical behavior for the healthcare professionals who participated in our programs.


Michael Carrese: That's great. Sticking with education, Dr. Neilan, I want to connect with you on that question, because this is a constant theme you hear, that patients have, as I mentioned at the beginning, these long, sometimes very frustrating experiences getting diagnosed. It begs the question about what's happening in medical school and medical education. Can you talk about that a little bit?


Dr. Edward Neilan: It's difficult to diagnose rare diseases for a combination of reasons. One is the rarity of the conditions. When I was a medical student, I heard—and I believe it based on how thick a medical dictionary is—that the average medical student learns forty thousand new words in medical school. You also learn a tremendous amount of other information. 


I remember my roommate, a brilliant fellow, who's now a full professor of Neuroscience at Washington University in St. Louis, once walked into my room while we were both studying separately, and he said to me, "Ed, I think I finally understand why they want us to learn all this stuff"—by which he meant tiny little details about drugs and bugs and bones. He said, "They don't really expect us to remember it all, but if you see it, maybe it'll come back to you." 


There is that scope of information. Nobody can really know all the diseases, let alone all the rare diseases, of which there are now estimated to be seven thousand. The average physician sees few tens of thousands of patients in their professional career. If a disease has an incidence of 1 in 100,000, in a full career, you're probably never going to see it. The sheer rarity of it makes it difficult. 


Another thing that makes it difficult is that most diseases either present in a gradual fashion, or at least have a milder form that presents in a gradual fashion. The first time you see a patient experiencing some difficulties due to their rare disease, they may be showing only a part of the picture of that disease. A few years later, they may have manifested more fully and it becomes potentially easier to make those connections.


I think that there's only so much that physicians can have memorized in their heads. They have to have, number one, a willingness to be continual learners, and when a patient doesn't have a certain diagnosis that is a well-established diagnosis, go back to the textbooks and try and figure out what it is. The busy schedule of clinicians these days and the way that clinicians are reimbursed by formulas often doesn't allow time for that, so there are some systematic issues there. I'm sure there can be some improvements in education, but you also have to have some systems improvements, I think, to give people time to search for difficult-to-make diagnoses.


Michael Carrese: Rebecca, do you want to weigh in on that?


Rebecca Aune: Yeah. I always think about this when we are at medical meetings or conferences. Our booth is always very popular because we give away little zebra stress balls, and everybody asks, "Why the zebra mascot?" We explain that in medical school, when taught about differential diagnoses, students are taught, "If you hear hoofbeats, think horses, not zebras. Think about what this likely could be." 


Here we are, representing twenty-five million American zebras living with rare diseases every day. I think we've got a steep hill to climb in moving the needle, so to speak, on early accurate diagnosis, because patients and families are often living in a diagnostic odyssey for years, or are still undiagnosed and have no real patient advocacy home. We seek to be that at NORD for undiagnosed patients who know they're rare, they just haven't named the beast yet.


Michael Carrese: On the brighter side of things, Dr. Neilan, one thing that has helped a lot with the diagnosis is all the progress that's been made with genetics, which is, as I mentioned, one of your subspecialty areas. Can you characterize the impact that progress has made on helping with a diagnosis?


Dr. Edward Neilan: Yes. In 2001, after about a century of trying to map genes in humans and other individuals, the first draft of the human genome sequence became available. That first draft of the human genome cost about a billion dollars and took decades to generate. One of the most impactful things today in the rare disease field is that increasingly better DNA sequencing technology means that now, for a thousand dollars or less, I could sequence your genome. That means that we now have access not just to a few well-known diseases or genes that are associated with diseases, but potentially to the root causes of all genetic diseases.


Insurance companies currently are not always paying for this testing, which is a clinical frustration given that it can often shorten the diagnostic odyssey. That's one of the policy issues that NORD is currently quite interested in. But I think that's having an impact. This new technology generally is referred to as next-generation sequencing. I think you can expect many more diagnoses to be made through next-generation sequencing in the future. Genetic technologies have also now progressed to the point where we can either insert a healthy copy of a gene, so-called gene therapy approaches, or potentially even edit the gene to restore it to its normal function in place—so-called gene editing.


These technologies are newer. There are, I think, two gene therapies approved in the United States now, one that cures a form of blindness and one that dramatically improves an early form of inherited neurological disease. There's thousands of other diseases for which these technologies may be applied in the near future. I think that's the real revolution, combining rapid diagnosis with gene-targeted therapies that we see on the horizon.


Michael Carrese: I think revolution is not an overstatement in this case. Rebecca, I'm curious about COVID and how that has impacted your work at NORD. Also to the extent you can characterize it for us, how has it been impacting the patients that live with these conditions and their loved ones?


Rebecca Aune: Sure. Beyond the initial fear of not being able to get their medication on time and the shortages, we all knew about early in the pandemic of personal protective equipment, our patient organizations obviously had to send their employees home, cancel fundraising events, and their normal revenue streams that come in through grassroots fundraising. NORD was able to assist them with some grant funding to keep their doors open. 


For the patients and caregivers, first and foremost, what really strikes me to the

this day is the isolation on top of the isolation of living with a rare disease. Not knowing others—especially those not near you—living with your disease, struggling to find a specialist who can treat you, living with the day-to-day burdens of managing your health, and coping with life-threatening or life-limiting disease that others don't understand, is already isolating. 


However, I think our community is used to figuring it out as they go. They could not be more flexible because they have had no choice. They take it one step at a time and do what they need to do to protect their lives, or protect the lives of their loved ones. I think also the fear of leaving the safety of one's home was very real, especially for those who are immunocompromised in our community.


Due to their rare disease or its treatment, many were unable to continue receiving their routine care in the traditional healthcare setting. Once telehealth became the standard across the country, patients and families had to adapt to seeing a clinician that way and get over the stumbling blocks of technical problems and difficulties and work through the anxiety of adapting to something new. For families, especially without an internet connection at home or the bandwidth required for a video call with a clinician, they had to figure out how to describe what was going on over the phone without body language or without their clinician laying eyes on them.


That speaks to the digital divide we have in this country. Now, I think the benefits of telehealth have been made well-known, especially alleviating the need for lengthy and burdensome travel for families with complex medical issues, and who often require specialized equipment, to go see a specialist, or even in some cases, participate in a clinical trial remotely, which we've been learning a lot about as we go. 


Telehealth also allows for more consultation between clinicians and/or with the patient, which can support coordinated care models and help take really great care of our patients. Again, our patients and families were flexible and did what they had to do, but it really has been coping with a lot of fear and isolation.


Michael Carrese: Yeah. Those are themes we hear on the program frequently. As we're wrapping up here, Dr. Neilan, we always like to ask our guests to provide a little advice to our listeners, many of whom are medical students or early-career health professionals, both about getting through this still challenging time with the pandemic, but also approaching their career in health care. What do you talk to medical students about?


Dr. Edward Neilan: There's no doubt that a career in healthcare is rewarding but also challenging. There are many challenges—the scientific and technical ones—but there's also becoming, in a way, intimately involved in the lives of other people, and helping them during what might be a life-changing illness or moment. Working with families and patients who may have socio-economic challenges that are greater than your own. While all those things are challenging, the reward of knowing that you helped someone directly, I think, makes it all worthwhile.


I may be biased, but I'd like to think everybody should become a medical geneticist. That's not really going to happen and shouldn't. We need physicians working in other fields of medicine, but getting back to something that Rebecca said, while you may not remember everything that you've learned in nursing school or medical school or another allied health care training program about rare diseases, don't forget that amongst the many, many horses out there, there are patients whose real diagnosis, whose real problem is a zebra. If you can just keep that in mind, keep an open mind, regardless of the field of healthcare you're in, you'll be doing rare disease patients a good service.


Michael Carrese: That's a really great note to end on. I want to thank you both very much for taking the time to join us today, but more importantly, for the really important work that you're doing at NORD to support the patients and families with rare diseases, who are often going through some pretty difficult circumstances. Thanks very much for coming on the show.


Rebecca Aune: Thank you. 


Dr. Edward Neilan: Thank you.


Michael Carrese: I'm Michael Carrese. Thanks for checking out today's show. Remember to do your part to flatten the curve and Raise the Line. We're all in this together.