S5, E10: FOXG1 Syndrome: A Mom’s Mission

Mary Parker (00:00):
Did you know that Charles River has a sister podcast? Eureka's Sounds of Science. Hi, I'm Mary Parker, the voice of Sounds of Science. Starting in the fall, Vital Science will fold into Sounds of Science, forming a unified podcast. We look forward to sharing more scientific patient and advocacy perspectives on trending issues in drug discovery and development. You can subscribe to Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts.

Nasha Fitter (00:30):
This is a big reason I think that patient foundations are best suited to drive drug development, especially preclinical development because there is a sense of urgency because it's not just a job for us. When you have a child that is suffering in front of you, that is declining in front of you, that is dying in front of you, the sense of urgency to drive and to push forward is unmatched, truly unmatched. And it's a big reason why when I spoke at the White House, I really talked about patient foundations need more funding to do preclinical work because we're going to do it much faster than academia, which is where currently the majority of, well all of NIH funding goes to. I just don't think that there is anyone that is going to have more urgency than a parent trying to help their own child.

Chris Garcia (01:31):
When we talk about the families of rare disease patients, we often focus on the day-to-day challenges: medication administration, lifestyle changes, caretaking, but for certain parents it's even more than that. It's recognizing that if you want a cure to be developed for your child's condition, it means taking matters into your own hands. I'm Chris Garcia, and in this episode of Vital Science, we sit down with Nasha Fitter, co-founder and CEO of the FOXG1 Research Foundation. She shares the story of her daughter Amara's struggle with FOXG1 Syndrome, the grassroot efforts being led by her foundation and the community of parents driving research forward for this debilitating condition.

Todd Poley (02:15):
Welcome to Vital Science Nasha. We are honored to have you. Would you tell us about yourself and your family?

Nasha Fitter (02:22):
Yeah, thank you for having me. My name's Nasha Fitter and I have a 8-year-old daughter named Amara who was diagnosed with FOXG1 Syndrome, which is an ultra rare neurodevelopmental condition. I have two other amazing children and my husband, we live in the Bay Area and are excited to share our story with you.

Todd Poley (02:43):
Absolutely. We're excited to hear it as well. Would you describe your daughter Amara? What are some of the things that make her so special?

Nasha Fitter (02:52):
So she started having seizures pretty early on, infantile spasms at around seven months of age. And because of that, we were able to get her diagnosis pretty quickly. So our diagnostic journey was much shorter than many rare disease families. She is really a happy, lovely child. She's able to walk, which we didn't know would be possible, so we're really thankful for that. She's completely nonverbal, so she cannot communicate through words, although she does communicate very much through her facial expressions and trying to use her hands, et cetera. She does suffer from epilepsy and has some other medical conditions, and so that really keeps us on our toes. But she's really just a happy, lovely child and who has taught us so much our family.

Todd Poley (03:40):
Oh, I'm sure, I'm sure. So you are the co-founder and CEO of FOXG1 Research Foundation. And I know it's so near and dear to your heart because of your personal journey and Amara, it's a proof that the parents' passion can move mountains. Could you tell us the story of how that foundation got started?

Nasha Fitter (04:02):
Yes. So early on after I received the diagnosis, I started to look into what could be done. And luckily there's many other parents that were similar to me that had started foundations that I was able to learn from. And the real lesson was that we do have technologies today, genetic technologies that can be really disease modifying for our conditions if enough focus is placed, if you have the right preclinical models, if you do the right testing. And so for me as an entrepreneur, all I had to understand is that there was a way and start the foundation. So I didn't do it on my own. I did it with a group of other parents and scientists, including Amara's genetic counselor at Stanford at the time. And we put the foundation together and really began our journey of understanding more about the gene and really focusing on what we could do to cure the condition.

Todd Poley (04:59):
That's great. And FOXG1 Research Foundation or FRF, their mission is to accelerate research to find successful therapeutics for FOXG1 Syndrome and related neurological disorders. So what's driving this important mission?

Nasha Fitter (05:14):
For us? It's all our children, right? It's not money, it's not ego, it's just we want to give our kids the life they deserve and whatever that could be for each one of our children.

Todd Poley (05:28):
That's great. And when you think about what you had envisioned when starting FRF, has your vision surpassed your expectations?

Nasha Fitter (05:36):
It has been quite a journey, and when we started, we had a single vision. We thought, Hey, let's just try to get a gene therapy for our children. Let's band together. We're going to fundraise, we're going to get the science done. But over the years, our foundation has turned into so much more. One of the big realizations was as we're looking for the therapy of the future, we need to help our patient population. Today we are all struggling quite a bit, and so we have now provided tons of services to our parents. We have conferences that we hold for our parent community, and we've also become quite invested and integrated into the rare disease community as a whole. We do a lot of advocacy for rare diseases as a whole, and I wouldn't have expected any of that when I started this journey seven years ago now.

Todd Poley (06:27):
So I wanted to speak a little bit towards Amara and her diagnosis. When she was diagnosed with FOXG1 Syndrome at a very young age, and now at eight years old, her childhood journey has been one of, I'm sure, remarkable resilience and strength. So what led to her diagnosis and how has her experience shaped who she is today?

Nasha Fitter (06:50):
So when she was born, she was a completely healthy normal baby and we didn't anticipate any issues. She started to have delays in her cognitive development and many children develop late. So her pediatrician, after she missed her three month milestones and her six month milestones said, some kids just take some time, let's wait until her nine month or one year milestones. And for us, it is both unlucky and lucky – she started having her infantile spasms about a hundred per day, and that's what triggered her genetic testing. And she was able to get diagnosed through the epilepsy panel, but luckily FOXG1 was on the epilepsy panel at the time, otherwise we might've had to wait much longer to get her diagnosis and it makes a big difference. The second we got her diagnosis, all of her... A) we understood what was wrong, and B) all of her therapies, her physical therapies, her communication therapies, all of that got kickstarted and it makes a big difference to start that earlier on in the journey.

So we were very lucky with that. And since then, she is a very resilient child. I mean, she's been through hell and back on so many occasions where she's had 24 hours of seizures, she's had seizures that wouldn't break until we put her into an induced coma. She's been through a lot and she continues to be a happy child. And the thing with her is that when she's not happy, we know something is really wrong with her medically because her disposition is to be so cheerful and it is quite heartbreaking when you have a child and they're screaming and pain and you don't even know what is wrong with them. So it's been a journey for all of us to try to understand how to help her in the best way we can.

Todd Poley (08:33):
How has that sense of urgency shaped your role as a patient advocate? Not just for FOXG1, but for the many ultra rare diseases out there?

Nasha Fitter (08:45):
This is a big reason I think that patient foundations are best suited to drive drug development, especially preclinical development because there is a sense of urgency because it's not just a job for us. When you have a child that is suffering in front of you, that is declining in front of you, that is dying in front of you, the sense of urgency to drive and to push forward is unmatched, truly unmatched. And it's a big reason why when I spoke at the White House, I really talked about patient foundations need more funding to do preclinical work because we're going to do it much faster than academia, which is where currently the majority of, well all of NIH funding goes to. So I just don't think that there is anyone that is going to have more urgency than a parent trying to help their own child.

Todd Poley (09:37):
Absolutely. And let's talk a little bit about that. I did watch that segment and how emboldened you were to speak at the White House Forum. What was some of the feedback from those that were in attendance there?

Nasha Fitter (09:51):
It was quite amazing, and after it sort of went viral, to be honest, and I received so many emails after from patient advocates saying "we're with you, what do we do next?" And I hadn't really thought of a plan of what to do next. I had just gone there to talk about this really huge issue that we have where there is no funding opportunity for patient advocacy groups. I mean, there's literally not even a place for us to apply to for a grant. And there's a group of us now that are trying to do something to see how can we lobby congress, how can we think about, and it's not that we want additional funds, it's the allocation of funding. There's already a lot of funding going towards rare disease research. It's just in our opinion, not going to the right organizations that are driving curative treatments. And so there is some work on is it Department of defense? Is it the NIH budget? But how do we carve out funding for patient advocacy groups that are driving research disease modifying research?

Chris Garcia (10:58):
FOXG1 Syndrome is a rare condition caused by changes in the FOXG1 gene, which is crucial for early development. Despite being small, this gene plays a big role by controlling many other genes in the brain. The syndrome varies in how severe it is. In serious cases affected individuals face significant challenges like needing wheelchairs, feeding tubes, and experiencing frequent seizures. In milder cases, they might be somewhat mobile and verbal, but still have learning difficulties. Understanding how FOXG1 works could lead to breakthroughs in treating not just FOXG1 Syndrome, but also other brain disorders like Alzheimer's and Parkinson's disease. So research into FOXG1 has the potential to make a big impact on how we understand and treat various neurological conditions. Let's hear more from Nasha and how this research may translate to other diseases.

Todd Poley (11:50):
What are some of those other diseases that are opportunistic out there?

Nasha Fitter (11:55):
Yeah, this is why rare disease research is so exciting because it's really hard to find a cure for Alzheimer's. As we know, the amount of billions of dollars that have gone into this field, and we still don't have anything really curative is because there's so many genes that affect Alzheimer's, and one of them is FOXG1. There's so many genes that affect schizophrenia, one of them is FOXG1. Similar with different types of autism, different types of brain cancers. And the beauty of these ultra rare diseases is you have the single gene, you have the mutations, and you have a patient community that's affected. So you can actually try different drugs on this very small patient community, and if you find something that could be a target for a much larger disease. So we are really hopeful that if we can find something that works for FOXG1, it could really have an impact on these larger conditions.

Todd Poley (12:49):
Although there are supportive therapies available to help manage the symptoms of FOXG1 Syndrome, there's currently no cure for this rare disease. And FRF has therapeutic programs in gene replacement, ASO and CRISPR therapies. Can you tell us about the progress of these specific research areas?

Nasha Fitter (13:09):
Yes. The word cure is such a heavy word. We really think about it – in the beginning, we thought we're going to cure the condition and now we realize we're going to modify the disease as best as we can. Right now, our main program, our lead program is our gene therapy program. Now, luckily for us, FOXG1 is a single exon gene. It's very tiny. It could fit into basically any viral vector. We have had the most success out of our, we do have an ASO platform. We have a small molecule platform, but we've seen the most disease modifying impact in our mouse models, our animal models with our gene replacement therapy. And so that is our lead candidate right now. We're really excited about it In our animal models, we have seen full rescue of corpus callosum, which nobody thought was actually possible.

One of when I started speaking to pharmaceutical companies about FOXG1, they all came back with– "you know, FOXG1 causes a lot of brain abnormalities, and we can't rescue those." Actually what we're seeing is: you can rescue brain abnormalities, the brain is growing, the brain can be changed. We have seen full rescue of the corpus collosum. We have a paper published in Nature on that, and we have another publication coming out this year. So we're very excited by that. And we've also seen rescue of cognition and other the different tests that we've done on our animal models for our gene therapy. So we're really excited about that program and that's the one that we're pushing now and we're doing IND enabling studies for.

Todd Poley (14:42):
Oh, fantastic. Okay, great. Well, we'll be watching closely on that. I wanted to ask a little bit more about the resources and support that your foundation provides for FOXG1 families and communities. Could you speak on that?

Nasha Fitter (14:56):
Absolutely. We realized in this journey that we do need to provide support to families day to day as we work towards these disease modifying treatments. So we have support when a family is in the hospital with their child for a long period of time. We now have someone reach out to them to make sure they're okay. We send support to them. We actually did have a FOXG1 mother who committed suicide after her child was in the hospital for an extended period of time. So we're really watchful of that because of that. Also, we do have a counselor now on staff who is a FOXG1 mom, a social worker who families can reach out to schedule time to speak to her. We have resources to help parents manage the day-to-day symptoms. We have a Facebook group where patients and their caregivers can come and discuss different symptoms.

We publish a lot of data. We have our natural history study where we've been able to learn about the different clinical symptoms patients are experiencing, and we're constantly publishing and giving input back to our families. We have webinars that we produce now every so often. We have meetings, family meetings that come together, both in person and virtually. So we do a lot to support our community and take the community also along the journey of finding these disease modifying treatments. What I tell our families is that, look, it's not my job to find a cure for your child. We are all in this together. So whatever you can do, if you could do one small thing, if you could raise a hundred dollars, do that. If you could contribute to the foundation in any other way, if you could write up something about how to help with an IEP, which our children, our families have to go through with their schools, write something up and we'll publish it on our website. But this is a community effort. We all have to work together if we're going to drive this change.

Chris Garcia (16:47):
Ensuring access to therapies for rare diseases is a complex challenge, especially considering the limited availability and high costs associated with treatments. Currently, only a small fraction of rare diseases have dedicated therapies – just 5 percent in fact. This leaves a vast number of patients without viable treatment options. Despite promising technologies like antisense therapies, RNA therapies and gene replacement therapies, the situation is dire with one in every 10 individuals in the US affected by a rare disease, half of whom are children. Shockingly, a third of these children won't even reach their fifth birthday due to a lack of effective treatments. The gap between the prevalence of these conditions and the development of therapies is a pressing public health crisis. To address this, the focus must shift toward education and advocacy, particularly in the early stages of research and development. By bolstering community engagement and support, we can cultivate momentum for advancing potential therapies into clinical trials, ultimately ensuring that patients in need have access to life-changing treatments. Let's hear more about how we can foster this kind of approach in the preclinical phase.

Todd Poley (17:59):
How can collaborating with partners such as a contract research organization like ours help achieve these milestones?

Nasha Fitter (18:08):
I think collaboration with CROs is the future. Right now, as I've mentioned, the majority of funding goes to academic research. And the issue there is that academics are creative people. They like whitespace and they need to publish. And you can't publish unless it's a novel concept. And the truth is that drug development is not that novel. It's pretty boring. You have to do specific experiments and you have to do them in a consistent way, and you have to do them in a way that you can populate a filing, a regulatory filing for the FDA. This is not an area where academics excel, yet all preclinical funding from the NIH is going towards academia. And you look at patient advocacy groups like ours, and we are tasked with raising the millions of dollars necessary then to actually focus on our diseases. So I think the future, and this is what we're doing at our foundation, is to have a lean team and to partner with contract research organizations, which are basically mini biotech companies. And together you could build a virtual biotech that is completely laser focused on only conducting the experiments that are necessary for a therapy. And I think that is the future.

Todd Poley (19:21):
Yeah, mitigating your risk early on, right? With the end in mind is absolutely a key essential focus.

Nasha Fitter (19:27):
Exactly. I can give you an example. We have worked with many academics on our mouse models and there's a lot of interest in let's do different communication experiments on these mouse models. Let's have, you know, use iPad with these mice and see how they react after we give them drug. And the truth is that the agency doesn't require any of those tests. So why would you spend your money on those tests? Those are just open-ended, interesting questions that are great for a research publication, but the truth is the agency has really specific criteria and tests that you need to do, and you could do those tests relatively quickly and get that done and move on to the next stage in drug development. Yet I see many foundations getting stuck in these sort of interesting academic experiments and it doesn't drive drug development fast enough. So it's really a need, and I think this is where contract research organizations can play a big role.

Todd Poley (20:23):
Nasha, I wanted to ask you, I see that you're a co-founder and partner of Citizen. Would you explain a little bit more about what that is?

Nasha Fitter (20:31):
Yes. Citizen is a natural history platform, and I co-founded this after really thinking about and realizing myself through FOXG1, how difficult it was to collect rich clinical data on rare diseases. And without rich clinical data, you don't understand the natural history of progression, which means that you cannot fulfill an IND filing. You cannot select your endpoints correctly. There's a lot that goes into scientifically curing a disease that is related to understanding the symptoms that patients are experiencing. I was lucky. Our foundation was really lucky that we were able to partner with the Chan Zuckerberg Initiative and Tania Simoncelli, who leads their Rare As One program was a really big believer in finding innovative ways to solve these problems and rare disease drug development. And the other amazing thing about Chan Zuckerberg initiative is that the Rare As One program actually provides funding directly to patient advocacy groups.

And this is because Tania believes that if you give patients or caregivers funding, they're going to do more with that than any other party. So we were able to receive that funding and I was able to take that and use that as citizen to really build out the rare disease platform. We were able to do a pilot with FOXG1 Syndrome and a few other similar neurodevelopmental programs. We were able to prove that we could collect over 10 years of rich clinical data within months, and we were able to use that data successfully in research studies. So there's publications that are already out there, there's pharmaceutical companies that have licensed that data and used them to populate their I and D filings and have accelerated their drug development. And this really all started with that CZI grant, and I'm very passionate about the work we're doing at Citizen and our goal is to really accelerate drug development with real world data. And we're seeing that the FDA is amenable to using real world data in place of traditional data sources, especially in rare diseases. So it's a really exciting time and I'm really hoping that we can push through and help a lot of other rare disease foundations as well.

Chris Garcia (22:50):
Raising funds for the FOXG1 Research Foundation or any similar cause is a monumental task that requires constant effort. And unfortunately, traditional efforts like bake sales simply won't cut it when facing bills that can run into millions of dollars, such as the $8 million toxicology bill for enabling studies. The foundation has learned that tapping into philanthropic donors is essential. This involves reaching out to individuals and communities, leveraging personal connections and making a compelling case for support. While initial donations may be modest, maintaining momentum and demonstrating tangible results can lead to significant contributions down the line. This type of fundraising requires building trust and showing impact, but it's the most effective way to secure the substantial funding needed for groundbreaking research. Let's hear from Nasha on how this type of funding could impact the future of rare disease treatment.

Todd Poley (23:45):
What does the future hold for rare disease drug discovery and development?

Nasha Fitter (23:49):
I am a complete optimist. I think the future is extremely bright for three really critical reasons. Number one, we have a plethora of new technologies that are coming down the market that are not science fiction gene replacement, gene editing, RNA therapies. These technologies are now in the clinic and they're in the clinic for brain diseases, and that is really promising. So over the next decade, we're going to see more and more success stories, which is going to make the field even larger and more accessible, and we're going to see more companies starting. We already see really interesting entrepreneurs building platforms for ASOs and RNA editing, et cetera, and I think we'll see more and more of that. That's very exciting. The second part is just the advent of genetic testing. More patients are getting tested and that's growing the population – very exciting. And the third are changes within the FDA and that is coming through Congress who is getting lobbied by the population.

And so you're seeing the FDA now, there's actually a task force that has to publish a report on how can they look at rare disease drug development and those applications and what can they do to make those go faster? And we're already seeing a lot of changes in CBER. So I'm really excited about what's happening on the regulatory landscape with the way we currently do drug development for large diseases, we can't use that mold for rare diseases. We have to look at different types of endpoint selection. We have to look at the use of real world data and clinical trials. We have to look at how do we accelerate and go from a phase one to three trial in one. So these are things that are really, they're innovative, they're innovative clinical trial designs, and that is happening at the regulatory level. So I think the convergence of these three is making the future very bright, and so we will not have the current only 5 percent of rare diseases having a disease modifying treatment hopefully in the future.

Todd Poley (25:43):
What does the year look like ahead for not just FOXG1, but what about Amara? What does the year look like for Amara?

Nasha Fitter (25:52):
This is a very exciting year for both FOXG1 and Amara. For FOXG1, this is the year that we are doing our IND enabling studies with the goal of submitting an IND, our first IND application for a disease modifying gene therapy next year, early next year. So we have put in an application for an INTERACT meeting with the FDA. We'll see if we get that. And we're well on our way. We'll be conducting our toxicology work this year. So it's just really exciting because we've been working preclinically for so long, and so to now having a lead candidate to push towards an actual clinical trial that we are going to be able to control is just, it's momentous for us. And of course we're fundraising to make that happen for Amara. I'm seeing a lot of breakthroughs in understanding, and this is the year that we are really pushing different communication strategies with her to have her use her iPad and other devices in just a much better way to let us know what she's going through. So we're excited about that as well.

Todd Poley (27:00):
What do you hope your and Amara's legacy will be?

Nasha Fitter (27:05):
I think about this quite a lot. Number one is obviously we're dedicated to find disease modifying treatments for FOXG1 Syndrome, and we're not going to stop just with our gene therapy. We're going to continue and continue and we know that our foundation is going to have to exist forever really, because even once someone has a treatment, they're still going to need support. Then we'll have the issue that you brought up around access, and we'll have to then switch our gears to figuring out how to get that treatment to all FOXG1 children. So our team is really dedicated to helping the lives of FOXG1 children around the world forever, and that's a legacy that I hope will continue. And the second part is in my journey of FOXG1, we realized how difficult it was to access clinical data.

And clinical data is critical. If you want to find a cure for a disease, you have to understand what your patient population is experiencing. You need to have really good understanding of the endpoints you're going to select for your clinical trial. My background is in tech and data, and when I looked at the way that's currently done, it seemed that we could use technology to really innovate. So I'm also a co-founder at Citizen, which is a natural history platform for rare disease patients, and it is being used by over 80 groups now, 80 patient foundations. And so I also hope that our legacy is to create real changes in the way that real world evidence can accelerate drug development. Anything we can do to shorten that timeline is going to be critical. So that's really the legacy that I hope Amara and I can leave, and I've been blessed to get to know others in the rare disease community and be a part of this community. And I could tell you there's just no other community like it. It's a group of passionate, smart people, and we're just blessed to be a part of it, and we hope our legacy can be everyone's legacy.

Todd Poley (29:09):
You are a true leader in that space for sure. I know that there are so many Nasha Fitters out there, but it's going to be the ripple effect from just leaning in, being emboldened and using that passion for good. How can our listeners help you get there?

Nasha Fitter (29:26):
Well, number one, for any rare disease group, it's about fundraising. So, FOXG1research.org. I hope that every single person is thinking about their philanthropy and dedicating a percentage of it to a rare disease because rare diseases really need individual philanthropy. There is no other way that we're going to be able to solve these problems. So if any of your listeners are compelled to donate to FOXG1, we would love that. FOXG1research.org. And then any other ways that any of your listeners feel that they could help. We love partnering with people. We need more advice. We're open to any of that, so please get in touch with me and just follow our journey as well. I post on my personal LinkedIn page all of our steps, so I am excited that I get to have a front row seat in developing a real gene therapy, and I'm going to be constantly posting everything that we're going through and we are going to make all of our regulatory filings, all of our successes or failures public so others can learn. And so just follow our journey as well.

Todd Poley (30:34):
Nasha, it's really been a true pleasure. Thank you for sharing your story, Amara's story, FOXG1 Research Foundation. It's very, very exciting and we're very grateful for your time.

Nasha Fitter (30:47):
Thank you so much for having me.

Chris Garcia (30:51):
Nasha Fitter is the Co-founder and CEO of the FOXG1 Research Foundation. This concludes our fifth season of Vital Science. On behalf of everyone who's been part of this one, thanks for listening.

Mary Parker (31:03):
Did you know that Charles River has a sister podcast, Eureka's Sounds of Science? Hi, I'm Mary Parker, the voice of Sounds of Science. Starting in the fall, Vital Science will fold into Sounds of Science, forming a unified podcast. We look forward to sharing more scientific patient and advocacy perspectives on trending issues in drug discovery and development. You can subscribe to Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcast. Until then, thanks for listening.