Rare Disease Parents Create a New Model for Drug Development: Nicole Johnson, Co-Founder and Executive Director of FOXG1 Research Foundation

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're bringing you the latest installment of our Year of the Zebra series. For those of you who may be unfamiliar, our Year of the Zebra work is an ongoing effort to educate millions of current and future healthcare professionals, caregivers, researchers, patients, family members, and the public about these zebra conditions. 

Recently, a baby at the Children's Hospital of Philadelphia with a rare genetic mutation received the first personalized gene editing treatment on a person of any age. This potential breakthrough comes on the top of hopeful developments in research on a variety of rare disorders, including cystic fibrosis, Huntington's disease, muscular dystrophy, and FOXG1 syndrome, which will be our focus for today.

FOXG1 is a rare neurological genetic disorder which causes severe seizures and impedes normal movement, speech, and sleep, among other problems. Fortunately, the FOXG1 Research Foundation is on track to begin patient clinical trials on a gene replacement therapy in 2026. 

I'm joined now by the co-founder and executive director of the FOXG1 Research Foundation, Nicole Zeitzer Johnson. Nicole is on a mission to find a cure for this rare disease for her daughter, Josie. She is joining us to walk through the state of research and to tell us about her efforts to educate parents, teachers, and students about disability inclusion through her Joyfully Josie book series and “Live Joyfully” education programs. 

Thanks so much for joining us today, Nicole.

Nicole Johnson 

Thank you so much for having me, Lindsey. It's so great to be here.

Lindsey 

I'd like to start our conversation today with just learning a little bit more about you and your life.

Nicole 

Thank you, yes. So I'm Nicole Zeitzer-Johnson and I am the co-founder of the FOXG1 Research Foundation, which I started in 2017 because my daughter Josie, who is 13 years old now, was born with a severe rare disease called FOXG1 syndrome. 

Previous to beginning the foundation and being in the rare disease world and the drug development world, I started my career in television. I worked for CNN for many years. And then my husband and I were part of a founding team of a music company, which we did for about 10 years. 

I always say everything in life leads you up to what you're going to need. So I learned how to be an entrepreneur and how to be very resourceful, and then when our second child, Josie, was born with this severe, rare disease, I had the tools to tackle it the best that I can and really make a difference.

Lindsey 

Absolutely. Thank you for giving us that background. I really liked what you said about the history and how your backstory kind of prepares you for the future. I want to shift gears a little bit and talk about Josie and your family's journey with FOXG1 and when it started.

Nicole 

Yeah, well, when Josie was born in 2011, everything seemed fine. And then as a few months went by, she just really wasn't developing the way children typically develop. She has an older brother, Tanner, who's about five years older than her. So I knew what to look for. And months went by, she wasn't developing. At the time, FOXG1syndrome just really wasn't well known, so it took us two years to find her diagnosis. 

I always say we're on a diagnostic odyssey. Fast forward to today and children are getting their diagnosis a lot faster. So, FOXG1 syndrome is a rare severe neurological disorder. It causes many disabilities and medical complexities. So Josie is 13 years old. She is in a wheelchair. She cannot walk. She can't even sit up really without falling over. She can't talk. She's fed with a feeding tube. She has epilepsy, which right now is under control. You know, it's tough. Josie has it tough, but she is just the most joyful, amazing little girl in the world. 

And I know that she understands things. We have discovered ways that we do communicate, which is a really interesting story, but we're very connected. I know that Josie is smart. I know that she understands everything. Can you imagine how frustrating it is to not have the ability to express what you're thinking, not be able to say help, not being able to say I love you, but wanting to?

I wrote the children's book Joyfully Josie, which really embodies that despite all these disabilities, Josie is just the most joyful little girl, and that book was written to advocate for disabilities inclusion. But really, Josie has been my inspiration to do everything I possibly can to change the face of this disorder, not only for her, but for every child in the world today and in the future who have FOXG1 syndrome. And that's what we're doing.

Lindsey 

That's incredible. You said something there that I want to come back to. I know we're going to get to the book here in a little bit and the foundation...but you said something about how you're able to communicate. Can you talk a little bit more about that?

Nicole 

Yeah, yeah. Josie has tried the different communication devices that are out there for children who can't speak. She does have a communication device that she uses in school and uses at home where she hits buttons guided by an iPad, and she does okay with that. Hitting buttons is not the easiest thing for her because of FOXG1 syndrome. It's hard for her brain to tell her body what to do. So with a lot of practice, she's getting better at purposely hitting the button at the right time. However, I discovered -- and I discovered this through a mother of another FOXG1 patient -- what's Josie's point of access? And she showed me maybe Josie can lean correctly. 

So she sat Josie up in front of me and she said, “Josie, if you lean to the right, it means yes. If you lean to the left, it means no. Show me yes.” Josie leaned to the right. “Show me no.” Josie leaned to the left. Then we started putting words up in front of her. Which one of these -- and I had the word home and boat -- which one of these do we live in? Josie leaned to house. We put math equations in front of her and Josie leaned to the right answer. 

So this opened up our world of communications because I could just sit her up on her bed and say, does anything hurt you right now? Yes or no? So every morning before she goes to school, I run down a list of questions of the things that I may need to know and I've identified when she has a headache, when she does need pain medicine, when she does

doesn't need pain medicine, when she's not happy about something. So finding this point of access that's Josie's has been incredible.

Lindsey 

I love that story that you shared there and the fact that you're learning from other parents of FOXG1 children. I know it takes a village and I know we've heard from other zebra parents about leaning on other parents and learning from them and what they're kind of going through. So I love that you shared that. I want to talk about the research foundation. I understand the inspiration for it, the crucial work that goes into it. But wanted to see if you can give us an overview of the incredible work that you guys are doing there.

Nicole 

Thank you so much. We are at such an incredible time in our journey as the FOXG1 Research Foundation. When we founded the foundation in 2017, there was very little known about FOXG1syndrome. Josie was actually the 92nd person in the world known with it. Today we know of over 1,200, but back then there was very little research. There was no concerted research strategy underway. 

So, we put together this foundation with parents from around the world and we said let's start. We put together a scientific advisory board and a scientific strategy to create models that replicate the disease. So what we did is we went out and we spoke to biotech CEOs and pharma CEOs and said if you were to ever pay attention to FOXG1syndrome, what would you need from us? And they told us you're going to need assets, you're going to need mouse models, you're going to need IPSC lines, you're going to need assets to test any research that you do, any potential treatment on. You're going to need the natural history of the disease, you're going to need a patient registry. 

So we did the work back approach and we just made all of those things happen. And we were innovative at every step of the way because as parents, we realize, you know, the way traditional drug development is done is really not going to work for us because we're an ultra-rare disease. We looked at the model for traditional drug development, which is about 31 years to bring a drug to market and $180 million. And at the same time, we're living in this scientific renaissance when genetic therapies are fixing diseases. So we have these North Star rare diseases to look towards like spinal muscular atrophy that has a successful gene therapy for children. So we know that gene therapy is only on the rise. But for an ultra-rare disease, you know, 31 years and $180 million is not practical.

So, we've pioneered a new model for rare disease drug development and we have brought those numbers down to instead of 31 years, 12 years and instead of $180 million, we found a way to do it for under $25 million. A lot of this has to do with a new model for natural history studies that we have pioneered. So as parents dedicated to getting a treatment our children in their lifetime, we have sort of turned the rare disease drug development landscape upside down and created this new model that helps accelerate treatments not just for FOXG1 syndrome but for rare diseases at large.

Lindsey 

It is such impactful and important work that you guys are doing here, and the foundation is definitely proof of that. I thought that I had read somewhere that the foundation is on track to start a patient clinical trial next year. Can you talk a little bit about that?

Nicole 

Yes. So this is so exciting. So like I said, we started the FOXG1Research Foundation with, you know, just scratching the surface to understand the biology of the gene. Today, we are on track to bring a promising gene therapy into patient clinical trials starting early 2026. So this is just really amazing. We are moving swiftly along the FOXG1 gene therapy roadmap. We are having very favorable conversations with regulatory agencies and moving through the roadmap, which is right now toxicology manufacturing and moving towards clinical development, which will begin early next year. 

It’s amazing that we're starting these clinical trials next year, and the goal is to get this gene therapy to the children with FOXG1 syndrome all around the world.

Lindsey 

It's incredibly exciting to see the progress happening here and we're going to continue to watch this space. You mentioned something earlier about how some of treatments for one rare disease have an impact on others. I wonder how the work that you guys are doing right now for FOXG1 research can impact other rare disorders.

Nicole 

That's very much a part of what we're doing. While we're parents here to give our children the healthy lives that they deserve, this work that we're doing is, you know, it's not only near term because we're starting these clinical trials soon. This is gene replacement therapy that has the potential to really improve lives, but it's far reaching because of this model that we've pioneered, which is parent-led drug development in action. You know, this model has the potential to help pave the way for many other rare diseases.

Rare disease is not a rare issue. There are more than 10,000 rare diseases affecting more than 300 million people in the world, half of which are children. And the issue is that only 5 % have a treatment. And the thing is, if you are a single identified gene, like FOXG1, if your disease is caused by a single identified gene, it could potentially be fixable. With gene therapy, what we're seeing is that these single identified genetic disorders are fixable. We are fixing the disease at the place of where the mutation occurred with gene editing. Gene replacement therapy is what we are doing. 

But the problem is we have a population of only 1,200 people who have FOXG1. It's just not lucrative for pharma. So what is a parent led organization to do? We're doing it ourselves. So we're actually making history as the first rare disease foundation that is sponsoring our own clinical trials. Without having a pharmaceutical company saying we'll sponsor your trial or government funding, we're sponsoring it ourselves. 

We're sponsoring multi-site full clinical trials for the FOXG1 gene therapy through the power of philanthropy. This is why every single dollar donated helps so much because we are able to drive this through clinical trials ourselves, and this is a model that could potentially help other groups like ours to follow in our in our footsteps so when you don't have a pharma savior to take this promising treatment through trials, there is a model to do it yourself. 

In fact Josie and I were featured in a Bloomberg article that was called “When a Miracle Cure is Left on the Shelf. What are parents to do?” And it's exactly about this. So we're seeing this rise of genetic therapies and the promise of them, but the issue is funding. So if we can do it in a shorter amount of time for less money, we can get more treatments to more patients who need them.

Lindsey 

Parent-led drug development, sponsoring clinical trials is fascinating. I'm really excited to see where this goes. I know with our work with Year of the Zebra, we've seen firsthand how collaboration and shared insights can really accelerate advancements across the entire rare disease community. I want to give our listeners an opportunity to go and find out more about the incredible work that you and your team are doing. Where can we direct them to?

Nicole 

Thank you so much. Yes. So our website is www.foxg1research.org and we have launched the Yes They Can campaign to drive our gene therapy through clinical trials to approval. So you can find the Yes They Cancampaign on our website through our gene therapy page. And we named it Yes They Can on the premise that our children can live healthier lives. 

You know, as parents we were always told, they can't walk, they can't talk, they can't do this, they can't do that. Well, why don't we change that and say what they can do. So thank you for asking that. We also have www.FoxG1GeneTherapy.com which will bring you right to the gene therapy page on our website.

Lindsey 

Amazing. And we'll be sure to list those for our listeners. I want to switch gears and talk about you as an author. I actually recently received -- I've got it right here, -- my copy of Joyfully Josie. It was an incredible book and I want to give you an opportunity to tell us a little bit about how this came about.

Nicole 

Thank you so much. So, as Josie's mom, I found myself having the same experience over and over. You know, I would bring Josie to the park or bring Josie to the local ice cream party where all the kids are together and I realized that young children, when they see Josie, they're afraid. They look at Josie -- who's older than them very often -- and she's in a wheelchair. She's not running around. And if they try talking to her and she doesn't say anything, or she might be laughing, young children kind of look at Josie with this deer in headlights look and I think their parents are also uncomfortable in those moments. They don't know what to do. 

Sometimes their parents tell them, don't look, and the kids just run away. They're young and they're having fun with their friends and I don't blame them. It's just that they don't know what to do, and very often it's the first time they're seeing a child with severe disabilities. 

I remember it was the middle of the night and I was thinking, parents need the tools and educators need the tools to introduce disabilities to young children, and books and stories are experiences. So, I woke up in the middle of the night and said, “I'm going to write a children's book.” I sat at my computer and it just poured out of me. 

I wanted to write this book so that it gives the child the experience of meeting Josie at the park and seeing this joyful little girl and that there is a way to communicate with her. In the book we talk about the use of buttons...that Josie can hit the “yes” or “no” button and that there's a little boy at the park who sees Josie but he's nervous to go over to her -- which is the common experience that children feel -- but he does go over. He takes that step to find out how he could be inclusive. 

The book is called Joyfully Josie because, you know, Josie shows that although she cannot play like the other kids at the park, she's still so joyful. And I've kind of created this mantra around the book called “Live Joyfully” that I'm hoping to make synonymous with disabilities inclusion, much as “Choose Kind” has become synonymous with anti-bullying. 

Disabilities inclusion needs a mantra and “Live Joyfully “is that mantra because not only does Josie choose to live joyfully, but other children can help others live joyfully by being inclusive.

Lindsey 

I do think these stories are making a huge difference for children and families. As I mentioned, I read it to my three this past weekend and they really enjoyed it as well. Where's the best place for our listeners to purchase the Joyfully Josie book?

Nicole 

The best place is www.joyfullyjosie.com and the reason why it's better to buy it straight from the website rather than Amazon is because on the website, all the proceeds go back to the FOXG1 Research Foundation. So by spreading disability awareness, rare disease awareness, disability inclusion awareness, you are also helping to support a cure for FOXG1 syndrome.

Lindsey 

Amazing. And we'll be sure to share all these links here at the end as well. So at Osmosis, we are an education platform and we have many students and early career health professionals in our audience. I wanted to know what your advice is for them with working with patients and families dealing with rare disorders.

Nicole Johnson (22:45.587)

Yeah, thank you for that question. I think it's the most important question in my life. So really listening, you know, really, really listening to families and what they're going through and ways that you could support them that are actually helpful. Offering resources, offering community, offering ways to focus on what a child can do rather than what they can't do. Just like how finding Josie's point of access turned our world upside down. I think one of the most important things is connecting families with their own community. It is really a game changer. 

In addition to writing the book, Joyfully Josie and having the FOXG1 Research Foundation, I also launched an education platform called “Live Joyfully Education” where it connects the book to professional development courses for teachers, for them to get continued education credits. It's all centered on disability inclusion and really helping educators learn how to bring disability inclusion into their classroom and weave it through curriculum. 

We do in-person workshops, we have online professional development, I do assemblies reading Joyfully Josie to elementary schools around the country, which has been the most rewarding experience of my entire journey and my entire career. I stand in front of an entire audience, an entire elementary school, and I read Joyfully Josie, and then we engage in a 

Q&A, and children then have the opportunity to connect their own experiences to who they know who has a disability, and how they've included children with disabilities. I had an experience where one little girl raised her hand and shared with everyone that she has autism. I get a lot of the same questions because children are curious, so giving them the safe place to answer the questions has been a really, really wonderful thing. 

One of the most rewarding things about Joyfully Josie is when parents tell me, I read the book to my child and then one day we were at Target and they saw somebody who was either blind, or they saw someone in a wheelchair and they said, “Look, mommy, it's like Josie.” And then they went and tried to, you know, just have more empathy. You know, whether they are inclusive or they're just showing empathy, the fact that it's working is incredibly rewarding.

Lindsey 

There's so many good pieces there to pull out, such great advice. The ones I think that I'll kind of repeat is just really listening to those families, supporting them in helpful ways, providing them with additional resources, tools, and a sense of community, and just reminding everyone to show empathy in their day to day.

Nicole 

Yeah, I think empathy is the key word. You know, my advice to those working with families with rare diseases and medical complexities is to lead from the lens of empathy.

Lindsey 

Exactly. One of our core values at Osmosis is “starting with the heart” and I think empathy ties in just beautifully with that. 

Before we wrap up today's episode, I wanted to give you an opportunity to mention anything that maybe we didn't cover here.

Nicole 

All of our focus is on driving this gene therapy to patients worldwide. We have FOXG1 Research Foundation affiliate chapters and foundations in six other countries, so this is really a global effort. And we say, this work that we're doing is for children today, children who are going to be diagnosed tomorrow, and children who aren't even born yet. 

So, for anybody that joins us on this journey, the impact is so, it's so meaningful. It's so big. We invite you to walk this journey with us, and thank you in advance for that. You know, I kind of had this joke with my team that there should be like a Tinder app for philanthropists who are looking to support causes where they're going to see a real impact and it's going to make a real change. So, we have our story and we're going on a philanthropy roadshow, sharing our presentation, sharing the impact of support with anybody who's maybe looking for us. That's sort of my Tinder analogy. Like, who is the foundation that is doing this as efficiently and innovatively as possible and really going to radically improve children's lives? 

So if anyone wants to reach out to me and see our presentation, that would be so wonderful because it's through philanthropy that we're able to get this work done.

Lindsey 

Thank you so much, Nicole, for sharing your inspiring story and the incredible work that you're doing at FOXG1Research Foundation, “Live Joyfully” education and your book series, Joyfully Josie. Thanks so much for being here today.

Nicole 

Thank you so much for having me and thank you for your zebra series and what you do, and the mantra of lead from your heart.

Lindsey

FOXG1children all have one thing in common: they're amazing. Despite their challenges, just like Josie, they show us how to appreciate the little things in life and teach us about strength, love, and pure joy. I encourage you to check out the FOXG1Research Foundation. It's a group of scientists, doctors, and families who are all working together to find a cure and bring hope and healing to children around the world. It's clear that through innovation, advocacy, and education we're making meaningful progress in the field of rare diseases. We hope you continue following along with us as we continue our work with Year of the Zebra, and we continue to make progress for our families and patients like Josie, who are impacted by FOXG1syndrome and other rare disorders. 

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