A Transformational Time for Rare Disorders is Coming: Dr. Jessica Duis, VP of Clinical Development at GondolaBio

Lindsey Smith

Hi, I’m Lindsey Smith, welcoming you to Raise the Line with Osmosis from Elsevier, an ongoing exploration about how to improve health and healthcare.

Today we feature another installment in our Year of the Zebra series, an initiative dedicated to spotlighting rare diseases and encouraging clinicians to look beyond the most obvious diagnosis. Year of the Zebra is a powerful reminder that while common conditions often account for the most common symptoms, we can’t overlook the “zebras,” those rare but impactful diseases that, when recognized early, can change the course of a patient’s life.

Throughout this series, we’re working to elevate awareness of these often-missed conditions, equipping clinicians and students with the knowledge to spot them sooner and improve outcomes for patients who too often go unheard. For those of you interested in learning more about Elsevier’s Year of the Zebra, we’ll put the link in the episode description.

As we continue our Year of the Zebra series on rare disorders, I’m happy to welcome Dr. Duis to the podcast, whose diversity of experience and expertise allows her to provide insights on a wide range of topics in this space.

Dr. Duis is a geneticist, pediatrician, and special-care physician with a focus on the management of individuals with complex, rare disorders. Her career has bridged academia and industry and includes work in gene therapy, neurogenetics, neuromuscular conditions, and metabolic disorders with a special interest in chromosome fifteen disorders, such as Angelman and duplication 15Q syndromes.

As an academic, she developed several centers of excellence focusing on clinical research and drug development. She also ran several clinical trials before coming to industry, where she is currently the VP of clinical development at Gondola Bio.

Thank you so much for joining us today, Dr. Duis.

Dr. Duis

Thank you so much for having me.

Lindsey Smith

So, let’s jump in. I’d like to start learning more about you. What first got you interested in medicine?

Dr. Duis

My interest in medicine started when I was very young — actually when I was eight years old. I had declared that I wanted to be a doctor, and I had one of those doctor kits, so I would wear a stethoscope all the time as if I was a doctor.

And then as I got older, I had a much younger sister and was very interested in some of the differences that we were seeing in my sister, particularly with respect to her weight. So that got me really excited about biology and understanding metabolic and how things work in the body. Then I continued to volunteer and spend time in the hospital, really loved babies, and knew I wanted to take care of children.

Just before I went to medical school, I spent some time as a research assistant doing research on a couple of rare disorders in an MRI and Functional Magnetic Resonance Imaging lab and just knew that I really wanted to take care of people. One of the things that was really important to me is how accessible doctors are.

And so I noticed that, you know, in movies or when you read books, you would hear that doctors made house calls and were very accessible to everybody in the town. I sort of envisioned having that type of practice where I was very accessible, where I could be a part of the community, and so knew that I wanted to go into medicine from a pretty young age.

Lindsey Smith

That’s such a good starting point, and I love what you said there about it starting at age eight with a doctor kit, then moving into your interest in working with children, research assistant, and then finally entering medical school. Can you kind of take us through medical school and then what drew you to work in genetics?

Dr. Duis

Yeah, so I started out medical school thinking I wanted to be a neurologist and really focus on brain development in pediatrics. And then I liked everything in medical school — even ENT and surgery rotations — and one of the things that was really exciting was that I felt like genetics pulled all of it together.

So no matter what field it is, genetics gives you insight into how to administer anesthetics in surgery and how you take care of someone who has a change in their connective tissue so that you would do additional suture layers, what medications you can use for blood thinning. It had an impact on everything, and so it felt like it was a really good hub to sort of be a quarterback of care and really fit the model that I envisioned and even had on a pedestal as I was growing up — really connecting with families and having significant insight into a disease where you can sort of be the quarterback of care.

So I felt like it was such a good combination of all the things that I was interested in and so decided to transition to do pediatric genetics out of medical school.

Lindsey Smith

So, kind of picking up on that football theme and that team mentality that you have, I understand that at your clinic, you and your team take a very personalized approach to care, tailoring it to each individual patient and family. Patients also have the opportunity to see eight specialists in a single visit, creating really a one-stop shop and team experience.

And I think that’s really powerful — that you continue to support your patients all the way through adulthood. Can you talk a little bit about the impact of that integrated model on patients and families?

Dr. Duis

Absolutely, so that’s something that I’ve been incredibly passionate about, and anywhere that I’ve practiced I’ve really worked to bring a very special team together that shares the same passion for providing the highest level of care to families and patients.

And so one of the things that I love the most about that way of working together is it not only brings the community together in a shared clinic, but also brings the providers together. So you truly have a team that has an expertise in that particular disorder.

And as I’ve brought teams together, definitely there’s been a lot of education of learning together about that particular disorder and how identifying aspects that previously had gone unidentified because you have so many eyes on that individual.

And then you have — if you bring together a team where there’s a commitment to thinking outside the box and considering what treatments, even medications that may not be approved for that particular indication, that you could use to potentially help the individual and the family — it’s so important to have that shared minds model of discussing care.

That really makes a huge difference for the family. I mean, we hear families say all the time, “I wish my doctors would talk to each other and help us coordinate care so that we all are on the same page,” and you don’t have physicians or medical providers recommending different treatments for the same thing, some of which can be in conflict with one another.

So it really brings the team together and comes up with that comprehensive plan for families to take with them, even if they don’t live locally, to kind of help the care locally follow a plan and work together.

Lindsey Smith

Thank you so much for sharing that. It sounds like the dream team to me, and such a great model for all patients and families alike.

So, you’ve mentioned previously that your goal is to ensure patients have access to transformational treatments. Can you talk a little bit about the main barriers to achieving that and what can be done to overcome them?

Dr. Duis

Yeah, I mean, so the first challenge that we see, particularly in rare disease, is that these disorders, you know, maybe collectively be common because so many people are affected by rare disease in general, but each one of them is pretty rare in and of itself.

And so, you know, particularly the ultra-rare diseases that affect — we know maybe a hundred people in the world who have them — it’s hard to get industry involved and interested in such a small population of individuals because a lot of these potentially transformational treatments cost a lot of money to develop.

So, you know, industry companies are businesses, and, you know, thinking about that piece can be — it can be challenging to attract industry to certain rare disorders, especially if they’re ultra-rare. So I think that’s one piece.

The other piece is you really do need to know something about the disease. So having adequate natural history and an understanding of how the disease evolves over time is very critical. And for both of these issues, patient advocacy groups have been incredibly savvy at working with academics or getting a treatment to a certain place where it seems feasible to partner with industry and then also working really hard to develop natural history studies so that they can be collecting that data that may be very important to streamline development of drugs.

The other challenges are that the typical way in which we develop drugs is really for common diseases. So, you know, it’s a long path through regulators. This is changing all the time, but it’s a long path through regulators and getting to the point of an approval.

And for a lot of the rare diseases we take care of, that’s just too long. Patients need treatment now. Families need support now. And so that also can be incredibly challenging, particularly when you’re developing a treatment for a disorder that — you know, the earlier you treat, the more effective it’s going to be.

So catching people at the right time, where we can have the most impact, is really a challenge.

And then also it’s a challenge to make sure we’re measuring the right things so that we can understand clinically how it’s meaningful that they receive the treatment, and that’s an area still that really poses a challenge.

So for many of these disorders, you know, when we talk about treatments, the pathway is still to have to have some kind of placebo arm or sham arm, and that can happen even when there’s adequate natural history data that’s been taken for many years. And that’s really challenging for families — to know that, you know, and to agree to participate in trials where they know their child may not get treatment.

Lindsey Smith

Yeah, and I want to come back to something you said there about patient advocacy groups. They’re doing incredible work and creating a sense of community, I think, there as well.

We’ve had the opportunity to talk to many of these groups and even parents of rare disease patients as part of our Hear the Zebra initiative. And what I found was interesting as well is just how knowledgeable these advocacy groups are — and even the parents, becoming kind of experts in their own right.

Can you speak a little bit to that?

Dr. Duis

Yeah, I mean, these parents are absolutely amazing — coming together, fundraising, raising a lot of money to put towards research, and putting together organizations, nonprofits that can vet research and make decisions about what to fund that’s very strategic for their communities.

And even so savvy that they don’t take no for an answer, which is amazing. You see these families working so hard for their kids or adults where they’re taking on starting companies so that these medications and treatments can come to the clinic as quickly as possible.

It’s very exciting and amazing to see how much these patient advocacy groups can do for their community. I mean, it’s really why we’ve seen a lot of industry coming into rare disease — how these patient advocacy groups have set up their community to be successful by collecting data, engaging clinics, and making sure that they have trial-ready clinics that can take on these studies and have the patients available to participate in the study.

So, it’s a key aspect of this culture of bringing treatments to rare disease. So really, the credit goes to these patient advocacy groups.

Lindsey Smith

Yeah, they’re incredible. I want to kind of switch gears a little bit and talk about gene therapies. I know you’ve worked on several gene therapies that are now approved or in the pipeline. What advice or insights can you share about navigating their regulatory process for drug therapies?

Dr. Duis

Yeah, I mean, this has changed a lot over time, and I’m really excited about some of the more recent changes. When we used to talk about accelerated approval, which is essentially a faster track to getting a drug approved and getting access to more individuals with rare disease — it doesn’t have to be rare disease, but in the case that I’ve been involved, it’s been rare diseases — you used to have to have a clear clinical endpoint associated with a biomarker or associated with an interim measure.And now there’s an acceptance of having a biomarker without knowing for sure that there’s an impact on a clinical outcome.

So, you know, the thing that I’ve seen be the most successful with gene therapy and the most important is identifying some of those downstream, either toxic substrates or biomarkers that can be identified to go for an earlier approval to get the treatment to more people as quickly as possible.So that’s probably the most exciting thing I’ve seen in terms of gene therapy.

And then over the last ten years that I’ve been working on gene therapy, there’s been a tremendous amount of work done on delivery of gene therapy. So when I first started working on it, really, it didn’t get to the places we wanted it — particularly when we’re talking about a lot of the diseases that I take care of, which affect the central nervous system. So, the brain and the way that the brain works.

And now we have a lot of tools in our toolbox in terms of selective delivery of gene therapy to where we want it to go, which is exciting because it will limit, hopefully, some of the common toxicity that we see with gene therapy, which can have significant impact on the liver and the heart — making them a lot more safe and making them a lot more successful in terms of successful treatment.

And so we’ve been seeing this play out, and more and more gene therapies are getting approved or coming to the clinic using some of those mechanisms of delivery, which I think are going to be game changers for gene therapy in general.

Lindsey Smith

That’s really exciting to hear. And like you said before, when we were talking about barriers, time is of the essence for these rare disease patients, and so the accelerated process for acceptance and approval is incredible. And we hope to see more of that. So, you’ve worked in both pharmaceutical industry and academic settings. Can you talk a little bit about the differences of those worlds and how you’ve somehow managed to succeed in both?

Dr. Duis

Absolutely. Yeah, I mean, they are very different. So, I spent a lot of time — most of my career has been in academia. You know, one of the great things about academia is that you can do many different things. So I love to teach, and I was teaching in the medical school, and I loved to have medical students and trainees in the clinic with me.

And I was able to do that education piece, and then starting these centers and kind of focusing and doing translational research — both in terms of development of, you know, thinking about clinical endpoints for severe disorders and even collaborating and working with others on translational therapies and gene therapies — was something that I was able to do from academia.

And so, you know, that’s a pretty unique environment that you sort of have. So you almost have so many different jobs — that’s almost three different jobs that you are able to do from an academic environment. But it’s also a resource-poor environment in terms of, you know, you’re very dependent on grant funding and support to be able to continue to build the research and convince people that it’s important, which is definitely harder for rare disease. And so those are some of the challenges that you face in academic medicine, especially right now.

And in pharma, I was developing a lot of different clinical outcome assessments and endpoints related to digital health technology. And of course, you publish that, but you don’t have so much your hands in things where you directly or very quickly impact a clinical protocol to be able to get it into the clinic.

And one of the things — you know, I love working for industry because there’s a lot of resources to be able to ask a question and get it answered in a timely way most of the time. Sometimes there are delays. And then, you know, to be able to think and develop protocols of what you think would be best for that community and working with a whole team where you have a shared goal and you’re working very closely together to think outside the box and develop what you think will be the best for patients to successfully get to an approved therapy is so exciting.

And so, I’ve really been able to do that — to try to push the needle in terms of what we’re measuring, why we’re measuring it, and how we get a treatment as quickly as possible to patients. And so that passion that I have to be able to successfully get the treatment to the patients as quickly as possible has really been successful in industry.

Lindsey Smith

Exactly. Thank you so much for sharing the review of the differences of the two fields. I think your passion is definitely something that shines through when you’re speaking about this.

I want to ask you a little bit more about the rare disease space, and as we’re looking into the future, what makes you optimistic about the future of the rare disease space?

Dr. Duis

I think it’s a lot of the things that we’ve been talking about. I think the future of truly transformational therapies — we’re just at the tip of the iceberg. And I think that as the technology improves, as we get smarter and understand when we need to treat and what the best treatments are and how they should be delivered, I think we’re going to truly start to see some transformation in the natural history of many rare diseases.

I think we’re also going to, hopefully, continue to see companies that are working in rare disease be more successful in this area and really drive how regulators think about making decisions in terms of bringing treatments to individuals with rare disease. I think that piece is so important, and the patient advocacy groups have done an amazing job with some of the listening sessions and working with regulators. But to have some successes under our belt, where we really see that transformation, I think is what’s going to capture people’s attention.

And I see that coming as we treat individuals younger and younger, as we’re more thoughtful about how we deliver therapies and making sure that they distribute where they really need to be to be successful — I think we’ll start to see more of that, and that gives me a lot of hope for the future of individuals with rare diseases.

Lindsey Smith
So just to kind of play that back — transformational therapies and success for companies that work in rare disease, which would be a win-win for everyone. We’re excited to continue to watch the rare disease space for sure.

So, where can people — our listeners, early medical students — go to follow the work that you’re doing?

Dr. Duis
Yeah, so I have a website, rarediseasedoc.com. I also have social media that you can follow this and LinkedIn as well. So people can follow these as we progress.

And then I would encourage also any families listening or individuals with rare disease to engage in their community. I think that’s also a great place to follow how things are going, what opportunities there are to support the community or to participate in studies.

You know, one of the things that’s so important is that we get the community involved, and in order to be able to complete these studies, really supporting education of the patient communities and engaging with them so that we can get these studies done as quickly as possible is going to be very key.

So engagement with your Facebook groups of your specific patient communities, patient advocacy groups — if there isn’t a patient advocacy group for the particular rare disease that your child or you have or your adult has, then, you know, thinking about starting one and really engaging the community can really bolster and support attracting interest and developing therapies as well.

So I think those are really important. And then, you know, there’s also some bigger organizations, umbrella organizations like NORD, that are worth following that engage with many of these communities.

Lindsey Smith
Those are great resources, and we’ll be sure to link those in the podcast description as well.

Speaking of community, you have involved the patient’s siblings along with the patients and have authored some children’s books for patients and siblings. Can you talk a little bit about those?

Dr. Duis
Yeah, so we have a series of books called — and some social media that we’ve done in the past to try to engage siblings.

That’s a really important piece to me, realizing that a rare disease diagnosis affects the entire family, and thinking about the health and well-being of siblings is incredibly important. Oftentimes, you know, when someone’s taking care of a child with a rare disease or an adult with a rare disease, it definitely takes up a lot of time, and we know that siblings have questions, want to feel included, and also want to feel special as well.

And so, you know, the goal of the children’s books is to help with explaining rare disease and really presenting it in a way that siblings often see rare disorders — as a lot of the positive things. These books are based on Angelman syndrome, and we hear constantly siblings say, “Well, my sibling is just so happy all the time, brings so much joy to everybody.”

So it’s also important to show rare disease in that light as well — of almost superheroes — and that piece of what they bring to the community is really important in how siblings look up to and still see those rare-disease siblings, but also addressing some of the questions they may have that they might be afraid to ask, as well as some of the social-emotional pieces of being a sibling.

You know, I think it’s really exciting. I talk to a lot of siblings and have some personal experience there, and I would say, you know, it’s amazing what siblings do. You know, a lot of siblings go on to be in the medical field or behavioral therapists, you know, really engaged and really passionate about making the day-to-day quality of life of people with rare disease better.

Lindsey Smith
Absolutely. Do you mind sharing the titles of those books with us?

Dr. Duis
Yeah, they’re all under Sibling Stories or Rare Sibling Stories.

There’s three of them available. One is Genetics: A Rare Sibling Storybook on Genetics. One is Making Memories. Then, so if you search those on Amazon, you’ll find them.

Lindsey Smith
Awesome. Well, we hope all of our listeners check those out for sure.

So, at Osmosis, we are a teaching and education company. We love to fill knowledge gaps. Is there a topic you think Osmosis should make a video about that’s of particular concern or of interest to you?

Dr. Duis
You know, I think one thing — and one of our sibling stories is about participation in a clinical trial, which I think is really exciting, you know, and something that is important to share with family members, classrooms — it’s not just for siblings of, you know, people who connect with individuals with rare disease — to talk about some of these topics.

I think it would be really great to do a video about different types of therapies and what it means to participate in a clinical trial, because I think that’s going to become more and more common as we continue, hopefully, to develop treatments and successful treatments for rare disorders. And I think there’s a lot of misinformation out there about what it means to participate in a clinical trial. I think that would be very exciting and show the progress that we’ve made.

Lindsey Smith
Indeed. And I think that’s a great recommendation — participation in clinical trials and the different types of therapies. We will definitely pass that along to our content team and keep you informed if it ever gets created.

So, most of our audience at Osmosis is students, early-career health professionals. I wonder if you have any advice for them that you could give about tackling the challenges that they’re going to face in their careers.

Dr. Duis
I mean, it sounds cliché, but probably “never give up” is the main one. I mean, I think we all face challenges in our careers that we don’t anticipate, but I encourage people to think of them as opportunities to learn and to grow and to keep pushing forward. I think developing that level of resilience is incredibly important for anybody thinking about going into medicine or industry.

Lindsey Smith
Thank you so much for sharing that. Before we wrap up today’s episode, one last question for you. Is there anything that we didn’t cover today in our episode that you think we maybe should have?

Dr. Duis
I think that — hopefully it came through — but just there’s so much to look forward to in the future. And I think keeping that open mind for what therapies really look like is super important.

So one of the things that I do in my practice is really think about different ways of tailoring treatments to patients. So it might not be a gene therapy or precision therapy that targets the specific genetic change, but just encouraging always thinking outside the box and being creative.

Because the most important thing that I found is that even just listening sometimes makes a huge difference and supports the quality of life of the patient and the family. And so I can’t encourage that enough. Sometimes it’s the little things that you’re willing to do to support a family, a sibling, a child that make all the difference.

And so never forget about that. I think everybody wants to be the one to develop the gene therapy that ultimately really is transformative in the treatment of a disease, but it’s important to know there are a lot of day-to-day things that you can do that really improve the lives of others.

Lindsey Smith
Thank you so much for sharing this with us today, Dr. Duis — your incredible journey, your insights, and your passion for advancing rare-disease research and treatment.

Thanks so much for being with us.

Dr. Duis
Yeah, thank you so much for having me.

Lindsey Smith
Your work exemplifies the importance of recognizing and understanding the complexities behind these conditions — truly the essence of the Year of the Zebra Initiative.

For our listeners, remember that staying curious and considering the less obvious diagnosis can make all the difference in patient care and patient outcomes. We hope you gained meaningful insight into the often-overlooked world of rare-disease patients.

I’m Lindsey Smith. Thanks for checking out today’s show, and remember to do your part to raise the line and strengthen the healthcare system. We’re all in this together.