S5, E02: Strength in Numbers

Bo Bigelow (00:04):
One of the hardest things about this and about the glacial pace, I would say, of rare disease research is that eventually you recognize that the cure or the treatment that you're working on is probably not going to be in time for your own child. I could be wrong, I hope I'm wrong, but my wife and I talk about it in terms of what if this isn't for Tess and for us? It doesn't make it matter any less. It doesn't make us work any less hard on it. It's just maybe a fact that Tess might not get this cure and that it might come later and not be for her.

Todd Poley (01:00):
Imagine welcoming a child into the world and knowing immediately that their path will be different. From an early age, they face physical challenges and are unable to communicate verbally. Determined to unravel the mysteries of their symptoms, you seek the expertise of specialists. Finally, a glimmer of hope emerges as one identifies a gene mutation that could explain it all. The catch, this mutation has no name and lacks any published research. Where do you begin to understand your child's condition? How do you connect with others who may share this rare journey? I'm Todd Poley, and in this episode of Vital Science, we talk with Bo Bigelow, the father of rare disease patient, Tess, about how he finally arrived at his daughter's diagnosis, the pains he took to identify and connect with other patients, and the fulfilling role he has now as chairman and co-founder of the foundation for Hao-Fountain syndrome.

Gina Mullane (02:00):
Well, welcome to Vital Science, Bo. It's a real honor and pleasure to have you here today.

Bo Bigelow (02:05):
The honor is mine. I'm really excited to be with you guys and so thanks for having me.

Gina Mullane (02:09):
Absolutely. So will you please tell us about yourself and your family?

Bo Bigelow (02:14):
Sure. Our daughter Tess is 13. She was born in 2009 and she has a rare genetic disorder called Hao-Fountain syndrome. It was so rare that it didn't have a name when we were first learning about it, and it [00:02:30] took us a number of years to get a diagnosis for her. But having her in our family has really changed all of our lives a lot. We just have reevaluated careers and goals and ideas and how we spend our time and everything. She has an older brother named Dana who's 16. And so it's my wife and me and our two kids. And we're just really, I guess forever changed by what's happened with Tess and what we've learned about [00:03:00] her and that's our life. It's zero dull moments as my wife likes to say.

Gina Mullane (03:09):
Well, I know our audience would love to hear more about Tess and what makes her Tess.

Bo Bigelow (03:16):
Yeah, she's a really sweet girl. She is nonverbal almost entirely. Every once in a while she'll bust out with a word just kind of out of nowhere, but she's been nonverbal pretty much her whole life. She's had a lot of challenges, a lot of things [00:03:30] relating to her GI system and her bones. She didn't walk until she was five and it just takes her a lot of work to do these things that come naturally and automatically to other kids her age. All along, she's just had to work 5, 10, 20 times as hard to make all these things happen.

But she just has a great disposition. She's really sweet. She loves people. She's really social. She's a big hugger. [00:04:00] I'll be in an elevator with her and if I don't keep her close to me, suddenly she will cross the elevator to a complete stranger and give them a big old bear hug. She just really likes people and doesn't have any sort of stranger anxiety, so she's always reaching out to people and trying to hug them or touch them, and she just is a really joyful kind of presence. So we're really lucky to have her.

Gina Mullane (04:27):
Sounds that way. Now, [00:04:30] you've found a really compelling way of sharing Tess's story and the journey that your family is on, and it's through your blog and podcast Stronger Every Day, and that's how we found you. We were very inspired by that. And so what inspires you to share your experiences and put them forth for the world to hear?

Bo Bigelow (04:56):
At first, I think making the show was more for me just to [00:05:00] process things and figure out how I was feeling about what was going on. So I started it in 2015 and at the time we didn't even have a diagnosis for Tess. It was just going to a lot of appointments, going to specialists all the time, orthopedics, GI, neurology, you name it. Going back, we live in Maine, we live right outside of Portland, Maine. So driving down to Boston a lot, seeing specialists and having a lot of doctors, scratch their heads and say, "I don't know what this is. I can treat this symptom, [00:05:30] I can treat this problem that Tess is having, but I don't know what this whole big thing is all about." So at the time we started, we had a huge question mark in our lives about Tess, about what was going on and why she had so many problems with so many systems in her body and why things were so hard for her.

And so initially it was just a way for me to sort of create an audio diary of this happened this week, here's what went down, we were in Boston, or Tess is having surgery for this [00:06:00] or just some really big events in our lives that were happening. And so that's how it began. And over time, some really amazing things started to happen. The first was that I realized it was a way for Tess to be seen and understood by people who weren't necessarily seeing her day-to-day. So people who are related to her, her grandparents, her aunts and uncles, people who live out of town, but care about her and love her, this was a way for [00:06:30] them to kind of keep up with her every week here, what's going on with Tess? What's the update? And it was just a way to share with them what was happening with Tess and have her be seen by them and understood by them.

And then another thing that happened is that other people who don't even have what Tess has would get in touch with me and say, you are telling me how it felt to go to this surgery in Boston and how painful it was [00:07:00] for Tess and how hard it was for your family. And we are doing the same thing. We don't have the disease you have, it's a totally different gene and a different everything, but it's still a rare disease and we're still doing the thing that you're doing. And just hearing your story is helpful for us because we know that we're not alone. We're not the only ones doing this kind of stuff. And so it's heartening to hear another person's story. And so over time, this motive that I had of making my own diary [00:07:30] has been about just sharing stories about Tess and making sure she's seen and that other people with disabilities, especially people who are nonverbal, are seen and understood, but also just to let other people know you're not alone.

This is a really hard thing to do and it's going to be hard all the time. And I'm with you, I see you, I'm going through what you're going through and please reach out to me is what I've said all along. And sometimes people do and I love that. That inspires me a lot to just hear [00:08:00] what other people are going through and how they're handling it and answers they've found. I love to get information from other people because I'm learning all the time about things I don't have, I always say on the podcast, I don't have all the answers, I'm just a guy who's just doing stuff. And so if you have the answer, I want to know it, tell me the answer because I'd love to hear it. And sometimes people do and I love that.

Gina Mullane (08:23):
I'm sure you brought a lot of comfort to people through all of those episodes. I have to ask you though [00:08:30] the title, is that true? Is that about you getting stronger every day or where did the title come from?

Bo Bigelow (08:37):
It's really about Tess. All along, she had a lot of issues with her bones. As I mentioned, she had hip dysplasia and she had low tone, hypotonia is another name for that. And I think there's so many people who have that. I remember before we got our diagnosis and before we knew what was going on with Tess we like a lot of people were just really [00:09:00] looking for a community, just anybody out there who could understand what we were going through. And if you don't have a diagnosis, if you don't know what your disease is, you see people have, they've got a pin for their lapel and they have an awareness day and there's a parade and a bumper sticker, and they have all those things. And when you don't have those, you feel really isolated and alone. And so you latch onto whatever you can.

And I would go to the Facebook group for hypotonia and had 200,000 people in it. And I think a lot of [00:09:30] them were people like me who just wanted a community of some kind and you say, well, my kid has this, and what are people doing about this thing? So this low tone. And so initially it was about Tess, about her trying to get stronger and just going to physical therapy every week and talking with physical therapists about, do you think Tess will ever walk? Could she ever ride a horse? Could she ever run? Could she ever do these things? And all along we've said, the only limits Tess has are the ones that you put on her. [00:10:00] So we always believed that she could do those things and now she is doing those things, which is wonderful. But initially it was about Tess getting stronger every day.

And over time I've really learned a lot from my wife. She is just an amazing person in terms of resilience. She lost her mom when she was in high school. She's one of eight kids. And so she helped raise her younger siblings and I think that experience really shaped her. And so during this time with Tess that we've had [00:10:30] Tess, I've learned a lot about being strong, about mental fortitude and about being able to recognize that there's so much in life that you're unable to control, but one thing you can control is your attitude and your approach about it. So I think in terms of that getting stronger every day, I really have, thanks to my wife.

Gina Mullane (10:54):
It doesn't sound like you set out to become a patient advocate, but based on what [00:11:00] you're saying here, it sounds like you probably are in doing many great things within your community. Do you see yourself in that way? And how do you think your podcast and the other work that you're doing is really helping to connect families?

Bo Bigelow (11:20):
I do see myself that way. You're absolutely right that I didn't set out to be an advocate. I think if you asked me back in the day, you want to be a patient advocate, I would've said, I don't have [00:11:30] time or energy. I'm already doing a lot of things and I don't have the bandwidth for this. But I think in a way, any parent who's dealing with rare disease doesn't have a choice. And being an advocate can mean so many different things. Because there are so many health issues, you're accessing insurance 40 times a year for your kid. Most kids who are healthy, they go to the doctor, they go to their checkup [00:12:00] around their birthday and maybe they have a sore throat in the winter, you go to the doctor twice. But when you have rare disease in your family, you're accessing insurance so much more.

And invariably you're going to run into some hiccups there and have to kind of fight with the insurance company and fight to get things covered. And so I know a lot of parents, a lot of caregivers have to deal with that. And that's advocacy. There's so much around school and about education. I practice disability rights law. And so [00:12:30] that's one of the things that I do just in my job is try to help families figure out what they need for their children and how they can get it from the district and when it's necessary to file a suit and proceed on the legal front. So that's another piece of advocacy. But I think also just really simple day-to-day stuff. When your kid is nonverbal, you kind of have to speak for them sometimes and you have to protect them and kind of make their wishes known when they [00:13:00] aren't apparent to other people. So I wouldn't have picked this to be an advocate, but I have become one, and I think it's part of my life now. It's just part of what I do.

Gina Mullane (13:12):
So something that people may not know about you, which I think is so interesting, is that you started the Rare Disease Film Festival, which evolved into The Disorder Channel in 2020, which is an unexpected path, I think, for someone that is a [00:13:30] lawyer by background, by training. So how was the channel born?

Bo Bigelow (13:35):
And so 2015 was when we first learned that Tess wasn't the only patient with this disorder. It still didn't have a name. It was still very rare. She was the eighth known patient in the world. And so we learned that there were seven others and that there was a lab at Baylor College of Medicine in Houston, Texas where they were working on her disease. So we found that out in summer 2015. [00:14:00] And then that fall I went to my first rare disease conference, I went to the Global Genes Summit in California. And while I was there, I was doing my podcast that year. I had started it in January 2015. And so when I was doing some writing, I was blogging, I wrote for The Mighty a little bit. And when I got to Global Genes, I met someone else, another dad who was doing the same stuff.

His name's Daniel DeFabio, and he was writing for [00:14:30] The Mighty also and doing some blogging. And he's a filmmaker and he had made a film about his son Lucas, who had Menkes disease. And so we connected on that front of, I'm doing creative stuff to kind of make my way through this and figure it out. That's my way of coping and kind of processing, and you're doing that too. And so let's keep in touch, let's support each other. Because one thing most people don't talk about with the rare disease conferences is it's almost all women.

It's a lot of moms, and there are very few dads who attend. [00:15:00] And so this happened to be another dad, and I was like, "Hey, another dad, let's talk. We should talk." So we kept in touch, and a couple of years later he reached out to me and said he wanted to start a rare disease film festival. He had made his film about Lucas and he'd submitted it to a bunch of film festivals and the film had kind of run its course through the festival circuit, and he didn't really have anywhere else to show it, but he wanted to create this festival to have a place to show [00:15:30] this short film about Lucas.

Todd Poley (15:35):
Knowing Bo was trying to locate other patients with Tess's condition around the world, his friend Daniel suggested he created a film about Tess's journey. In the midst of establishing his foundation and planning its first big fundraiser, Bo initially declined, but with Daniel's persistence and offer to help with the project, he ultimately agreed. Tess's film aired the festival that fall in 2017 in Boston. [00:16:00] The event drew people from all over the country to share their stories, some about fatal diseases, and also to connect with other filmmakers. Two years later, Daniel and Bo headed west hosting the festival in San Francisco and establishing a community on the West Coast. Invigorated by the event success, they plan to make it an annual event. The following year, the country shut down due to the COVID-19 pandemic, but they were determined to make something of the submissions they'd received. [00:16:30] Let's hear more from Bo on how he and Daniel ensured their community had an opportunity to share and connect from a distance.

Bo Bigelow (16:40):
So we just said, with COVID, will we ever be able to have a festival again? We don't know. So what can we do in the meantime? And Daniel's and my idea was to create The Disorder Channel to just have a streaming channel and start to build a collection of films based on all these relationships that we had with filmmakers who were making content about [00:17:00] rare disease. And so that's how the channel was born in 2020.

Gina Mullane (17:05):
Terrific. So what have been some of the outcomes, stories that you've heard or things that you've learned that the channel and the festival have kind of impacted the rare disease community?

Bo Bigelow (17:21):
The goal of the festival was always to spur collaborations among the stakeholders of rare disease. So that's patients [00:17:30] and advocates, that's researchers, clinicians, that's biotech and pharma and everybody else who provides services to those stakeholders. So it's a lot of different pieces, a lot of different people, and it's been my experience that those folks just don't talk to each other enough across diseases. And really, I think when it comes to finding cures and treatments, that's how it happens is you're at [00:18:00] a conference and you're getting coffee and somebody else is getting coffee at the same time, and you get to talking and you find out they work on something. It's not your gene, but it's in the same pathway. And they've had success increasing production, increasing expression of that gene, and it's affected the whole pathway. So what they're working on isn't directly on your gene or your disease, but it could certainly help you and their findings could be important for your group.

So you trade business cards, you keep in touch, and then that person is in your [00:18:30] tribe, they join your circle and then they're part of what you're working on. And then they care. They care about your disease and you can come to them with questions and you can ask them to work on research with you, to partner with you, to collaborate with you. So that kind of talking between silos is the greatest. That's what we need more of. We don't have enough of that. And so what was good about the festival is that it's bringing together people from all across different rare diseases. It's not just one [00:19:00] disease, it's Hao-Fountain which Tess have, it's Menkes that Daniel's son had, it's dozens and dozens of diseases. So everybody in the room is there for a different disease, a different purpose. They're watching their film, but they're there with so many other people.

And so that was always the goal of the festival. And what was great is that those connections happened right in front of our eyes. We watched those chance meetings happen, we watch people [00:19:30] getting coffee and trading business cards. We watch people agree to collaborate, let's start a thing together. You're working on your disease, I'm working on mine. Let's collab, let's share samples, let's do stuff. So that kind of stuff, really, I think makes a big difference and can change the way we approach rare disease, the way we approach thinking about cures and treatments. So that, I think, is one of the most exciting things about the festival. And as far as the channel, what we're really pretty juiced about these [00:20:00] days is that we're creating a lot of original content where Daniel and I are looking for people who have something to say, who are looking for a platform and haven't found it yet, but they have stories of their own.

They have a funny story, they have some humor around their rare disease experience, or they have a story that needs to be told that's about a treatment that's working or just something, a message that they want to get out there, whether it's about raising funds or finding more patients [00:20:30] or whatever. So we're finding all these people all over the country and all over the world who are stepping forward and saying, "You guys have a platform. I have something to say, let's make a show together." So we've come up with a bunch of different shows with these creators, and that's I think really exciting just to empower people and say, instead of starting a podcast and trying to build your network organically, let's [00:21:00] throw you on this channel and have you on thousands and thousands of TVs around the world and just get your word out there that way. And just kind of giving them that platform, I think, is really exciting just to see the power that the channel has and how that can help people.

Gina Mullane (21:18):
So let's talk a little bit more about the disease that Tess suffers from. It's a neurodevelopmental disorder caused by a mutation of the USP7 gene. Can you tell us more about it?

Bo Bigelow (21:29):
Yeah, [00:21:30] we're learning more about it all the time. Like I said, there were really very few patients to start out with. Tess was number eight in the world. And so, one of our big goals for our foundation has been to find more patients, just get more people to join our group and then find out about what they're seeing. And up to this point, a lot of what we know about it has come from just Facebook, a closed Facebook group for parents. And it's just anecdotal. It's just somebody will post a picture [00:22:00] and it'll be of their child's eyes. So there's these, I think the word is epicanthal. I might have that wrong. I'm so not a science person, but there's these folds in the eyes that are a kind of hallmark of our disease.

So a parent will post a picture of those folds around the eyes and say, "Hey, my kid has this. Does anybody else have this?" And so somebody from France will say, "Yeah, I have. Look, here." And they'll send a picture. And then a Dutch family will share [00:22:30] a picture and then a Brazilian family. And so then suddenly you've got 40 pictures from all around the world of people saying, yeah, the thing you say you have, we have that too. But it's not exactly scientific. It doesn't hold up to that scientific rigor that we really need. So one thing we're in the middle of right now is a phenotyping study, a formal study. It's taking place in Heidelberg, Germany through the world's foremost expert on our disease. A guy named Dr. Christian Schaaf. He used to [00:23:00] be at Baylor in Texas, but he's since moved to Germany.

And so he's hosting families for this multi-day study. And we went last November actually with Tess so she could be part of the study. And that's going to be the first attempt to really gather phenotyping data from patients on that scale. And what we hope to do is kind of get beyond just that Facebook level of stories and photos that are shared and really have some information about the phenotype. But [00:23:30] we're learning more about it all the time. We definitely are always looking to do more research and we have some research initiatives underway, so hopefully we'll know more soon.

Gina Mullane (23:42):
And so how does the mutation in the gene USP7 alter the physical state? What actually happens in that kind of genetic situation?

Bo Bigelow: 23:54 So the mechanism of the disease is something we kind of understand. [00:24:00] The theory at least, is that it has to do with recycling, with the recycling of proteins within cells. And so in healthy people, the USP7 gene marks different items in the cell to either be recycled or trashed, like disposed of altogether, just tags them and says, recycle, destroy, recycle, recycle, destroy, whatever, tags them all. And then the cell knows what to do with those materials and routes them to [00:24:30] the recycling center, to the trash center or elsewhere. And what the theory is about the disease is that if USP7 isn't working right, it's kind of like one of those dimmer switches on the wall, the little dial.

If you have a house from the 1980s, you totally have this in your house. It's called a rheostat, and it's the dimmer switch that lets you dial the light to just where you want it rather than on and off, it's a dimmer switch. And so [00:25:00] the way the USP7 rheostat works, it fine-tunes that recycling. So it works just right in healthy people. And the theory is that in people with the disease, the rheostat is broken, it doesn't work, that fine-tuning isn't happening. So those materials kind of build up in the cells and the recycling just isn't working the way it's designed to.

Gina Mullane (25:22):
And you mentioned one of the physical conditions is hypotonia. Are there any other physical attributes [00:25:30] that come along with the disease?

Bo Bigelow (25:33):
Yeah, everybody has an abnormal brain MRI. We're hearing that pretty much across the board. Nearly everyone has an issue with speech. Autism, I want to say is 50 or 60% of patients have autism spectrum disorder diagnosed. Epilepsy is prevalent. It's something that sometimes can be delayed like in Tess. For many years we thought, [00:26:00] everybody else is experiencing seizures, but we don't have that. We're lucky that's not happening to Tess. And then a few years ago she had her first seizure, so we said, "Okay, we do have seizures after all." So those are the big ones, I would say. Definitely some growth stuff too, like low growth hormone, low birth weight and short stature, that kind of thing.

Gina Mullane (26:23):
So how many cases of Hao-Fountain syndrome are you aware of? Bo Bigelow: 26:28 The actual prevalence [00:26:30] is unknown at this point, but we were just shy of 200 patients that we found in the world so far. I think we're holding steady at 198 right now. So we have found a lot more people and we're always looking for more people when we know they're out there.

Gina Mullane (26:45):
Yeah. And is there anything unique about the condition you think that is really only affecting patients with this disease?

Bo Bigelow (26:57):
That's the tough part because [00:27:00] Hao-Fountain syndrome looks really, really similar to a few other diseases, it presents a lot like Angelman syndrome, especially what I described about Tess before, how she's super cheery. She's just a really happy kid all the time. And so that kind of sunny disposition thing, that's kind of an Angelman hallmark as well. And so it looks a lot like Angelman syndrome. And when we were going through round after round of genetic testing early in Tess's life, she had some geneticists who are like, "I'm [00:27:30] pretty sure this is Angelman." And then it comes back negative. So it looks a lot like that. It also looks a ton like Prader-Willi syndrome, which actually is very closely related and along the same pathway. And so Tess actually has a lot of the symptoms of Prader-Willi syndrome, even though she doesn't actually technically have Prader-Willi.

So that's what's hard, I think is you start out that diagnostic journey and of the rare diseases, Angelman [00:28:00] and Prader-Willi, those are kind of the more common ones. Those are the ones that most geneticists have at least heard of. And so they test for those and when they come back negative, sometimes the geneticists just say, "I don't know what to tell you, those tests are negative and it's not those things. And so I don't know what this is." And that's what they told us. And so until you get, we got a whole exome sequencing through a grant, it was really expensive at the time, this was 2013, so [00:28:30] we would definitely not have been able to afford it, but we got this grant and we were able to map Tess's exome. And so that's how we got the hit of the USP7 mutation. But otherwise, I don't know how we would've found out if we didn't dig deeper like that.

Todd Poley (28:47):
USP7 is part of the MUST complex along with MAGEL2 and TRIM27. This complex plays a crucial role in regulating cellular processes and gene expression and modulates [00:29:00] the ubiquitin proteasome system, which influences protein stability and degradation. The MUST complex dysfunction has been noted in neurodevelopmental disorders such as Schaaf-Yang syndrome and Prader-Willi syndrome, in addition to Hao-Fountain syndrome highlighting its importance in normal brain development and function. Individuals with these conditions often experience intellectual and developmental delays, behavioral and emotional challenges, feeding difficulties [00:29:30] and obesity risk and low muscle tone. More research on the MUST complex is needed to fully understand its implications on human development.

Gina Mullane (29:42):
I'd really love to hear more about the diagnosis journey for a patient and their family. You mentioned it is hard to get a diagnosis sometimes. Are there things to look for that can help others recognize the signs?

Bo Bigelow (29:56):
Yeah, I think it sadly is typical. I hear a lot of stories from people who [00:30:00] have a long diagnostic journey or are on one or have decided that maybe it's not going to end for them, that they may never get an answer. I know not everyone gets one, and I know we're really fortunate to have gotten one. It's very common I think to struggle like this and to not know because no matter how intelligent you are, and even if you have a background in medicine, which my wife does, she's a gastroenterologist, you just don't know what you don't know. [00:30:30] You're not exactly hearing about the USP7 gene every day. It's not in the paper. It's not something you've ever really heard of unless you have a reason to. And so we were just in the dark. We were in this place that I call the cloud of unknowing because you're just so lost.

And the people that know this stuff, the genetics teams that you're working with, they tell you that they are in fact lost as well. They just kind of shrug and say, "I don't know what to tell you." And so [00:31:00] you don't really have anything else that you can do to figure out the answer. If you're not in genetics yourself and your team doesn't know what to do, what's next? It's really hard. And so for us, what it came down to was even getting the name of the gene that was mutated. So the whole exome sequencing happens and they compare Tess and my wife and me and they get this hit and it says the USP7 gene [00:31:30] is mutated in Tess, but not in Kate or Bo. So we know that that's the difference when we look side by side Tess versus the two of us.

And so we said, "Okay, great." So to the genetics team, we said, "Awesome. So who else has this? Where are they? How do we get in touch with them? Is there a nonprofit that we can donate to? What's next for us? What do we do now?" And they said, "We don't know. There is nothing out there about this thing. There's no papers about this disease [00:32:00] and we don't know of an organization that you can contact or join and we don't know of anybody else who has this thing. And we don't even know that this mutation is what's causing what you see in Tess. All we can tell you is this is the only difference. When you look at these three side by side, these three people, Tess has a mutation here, you guys don't. And that's all we can tell you." And so that was 2013.

And so even though we had technically solved [00:32:30] what the genetic difference was in Tess, it didn't necessarily mean anything to us because nobody could even tell us that that was a disease, that was even a thing. And so what I did in the summer of 2015, 2 years later, I was reading an article in the New Yorker by a writer named Seth Mnuchin, and the article was about another family like ours that had what they call an N of one. N of one just means [00:33:00] you think your kid is the only kid in the world who has this thing. You don't know of any other patients. You've looked high and low, you've stayed up late and Googled things, which is doctors tell you not to do that. And that's pretty much the first thing you do when you go home that night is get on Dr. Google and you try things in quotes, move the quotes around, put the whole thing in quotes, whatever, your gene, symptoms, whatever.

You've done all that and you still think you're the only one. So this article by Seth Mnuchin in the New Yorker was [00:33:30] about another family. This a guy in Utah named Matt Might and his son Bertrand had the only case of this thing. And so Matt is a computer science guy and he figured out a way to use the internet to find other patients. And he had a really specific set of instructions, a blueprint essentially about how to do this, how to do what he did. So I just followed his exact instructions. I created a blog post about Tess and I put in all the genetic lingo [00:34:00] that was part of our genetic testing from two years earlier and just put it out there.

And this was the beautiful thing is that in 2015, Tess was, she was still five, she wasn't yet six, and all around her were these lovely friends of ours and loving family of ours that had just been following her journey and caring about her and thinking about her so much for years that there was this pent-up energy and this [00:34:30] strong desire to just do something, anything to help her and us. And so when we did what Matt Might said and we created our thing and put it out there, there was this tidal wave of sharing that everybody did because for years there had been saying, can we donate somewhere? Can we do anything?

And we were shrugging and saying, I got nothing. There's nowhere I can send you. There's nowhere to write a check to. I can't tell you where to donate. I have nothing to tell you, but this you can do for me, this you could do to help us. Share this [00:35:00] thing about Tess and maybe we'll find one other person who has this thing. And so everybody did, they shared and they told their friends to share, and it just spread like that. And we'd had this two year cloud of unknowing of knowing only USP7 and not knowing anything about the disease.

And so we took a deep breath, my wife and I, and we said, "Okay, maybe we'll find one other person someday. This is the beginning of a journey. Let's see where this goes." And all that sharing [00:35:30] created this wave. And in less than 24 hours, I got an email from this guy Mike Fountain, who worked at a lab at Baylor College of Medicine, and he had found my post on Reddit where I had not even put it, but someone else had put it for me. R slash genetics I think is where he ended up finding it. And he shared lab space with somebody who had seen it actually. So it wasn't even he who had originally founded.

And so he sends it this email and says, "Hey, I saw [00:36:00] your post. I work on the USP7 gene. There are other patients, we should talk." And so that day, around the middle of that next day, my wife and I got on the phone with Mike Fountain and he told us there were seven other patients, and Tess would be number eight if she proves to have this thing. And it does have to do with the disease, and they know about it and they're about to publish the first paper about it that fall, September 2015, they're getting ready to publish. And so Mike [00:36:30] kind of let us know, you're not alone. This is a thing. You're not crazy. There are others and now you're with us, you're in our tribe. And so we're laughing and crying and hugging Mike through the phone essentially. And so that was how we found out about the disease. But there was a long stretch there between gene and disease.

Gina Mullane (36:56):
Yeah. Incredible. It sounds like [00:37:00] lack of diagnosis is definitely an issue. Is misdiagnosis common? Does that ever happen with this condition?

Bo Bigelow (37:10):
Yeah, I think it does. I think because, like I mentioned before, if you're eager to just latch onto a community and it matches up with your phenotype, sometimes you just jump into that group. So when we didn't know about Hao-Fountain and hadn't met Mike Fountain yet, would just lurk [00:37:30] around different groups that were similar, like Prader-Willi syndrome and Angelman syndrome, and what are those parents doing? For example, Tess has this thing called hyperphasia, and it means that she just eats nonstop, eats all the time that she has no off switch like we do. When you eat a lot and you feel like, I'm quite full, I've had enough to eat, you sense that, you know your appetite has been fulfilled, that you're satiated. Well, she doesn't have that off switch. If you let her, she'll just [00:38:00] keep eating and keep eating, keep eating.

So you have to draw the line and stop her and lock food away and keep food hidden and not just leave food out. So that's a huge Prader-Willi thing, hyperphasia. And so not that she was ever diagnosed with Prader-Willi, but when you don't know what else it could be, and it looks a lot like Prader-Willi, you just live in that world. And if there's an open Facebook group that's about that disease, you kind of jump in there and just you treat [00:38:30] those symptoms and you treat those pieces of your kid's thing, because that's all you can do, that's all you got. And so I think there's also some part of you that thinks, my geneticist was so certain that this was Angelman and it comes back negative, and maybe that's a mistake. Maybe it really is Angelman syndrome and the lab tests got corrupted or whatever, and it was a mistake.

And this really is Angelman syndrome. I don't know, your mind does [00:39:00] some interesting things when you're in that world. But I think that's the biggest challenge I think we have is that we look so much like these other diseases. And if I could just reach more people right now at this very instant that you and I are talking, there is a family like that out there that's like us that has been through a few rounds of testing. They've never heard of USP7 because why would you? And they're intelligent people and they're able to [00:39:30] do a lot of things and look things up and figure things out themselves, but they just don't know what they don't know.

So they're not looking up USP7 because it's just not on their radar. But if this show could somehow get to them and they listen to it or somebody they know listens to it and gets them to listen to it and they hear the symptoms that we see in Tess, then maybe that would get them to go to their geneticist and say, "Hey, can you check out USP7? Can you do a whole exome [00:40:00] sequencing? Can you do a microarray and just target this one gene?" And then we would find them and they would find us. And that's happening more and more all the time. But, I mean, this is why I just shout about Tess and her disease from the rooftops all the time because I want those families, I want to find them. I want them to join us, and I know they want to find us, and that's the only way is to just let them find out about us. That's the only way.

Gina Mullane (40:28):
The power of sharing. That's an [00:40:30] indomitable spirit here. So in addition to your blog, your podcast and your channel initiatives, you also co-founded the Foundation for USP7 Related Diseases. Could you tell us about the mission for the foundation and how it got started?

Bo Bigelow (40:50):
Sure. So that first year that we went to Baylor College of Medicine to visit Mike Fountain, to visit [00:41:00] Dr. Schaaf, that was in 2017, and that was our first family conference that year. That was our first time meeting other people in person who have this, who are dealing with this. And so some of the people that were found right before Tess and right after Tess, they were there and people came from France and from multiple US states. And that was a life-changing experience in the sense of sitting with people who already know [00:41:30] what you're going through. There was so much of the time, I remember at that conference where I had imagined ahead of time that we'd be talking a mile minute, do you see this? Did you do that? And instead it was the opposite. There was a ton of time where you're just sitting in silence because you already know.

They already know who you are and who your child is and you know who they are because you're living the same existence. It's a beautiful thing. And so we were really inspired meeting those people and wanting [00:42:00] to do some more after the conference. And so my wife and I, with another few of the families who attended that year, we decided to start this nonprofit. And from the beginning, our goals have been two, number one, to find more patients because we always want to find more. And the more that we have, the more power we're going to have, the more strength in numbers we're going to have, the more research can go forward, the more samples we can get. So got to find more patients and we want to fund some research that can lead to a cure or treatment [00:42:30] of this. And so we made a really conscious choice in the beginning not to do a lot with trying to support caregivers or issue grants to have people travel to different stuff.

I know there's a lot of other foundations that make different choices about that. We really wanted to just try to get to a cure and try to make research move forward and not think so much about those other pursuits. And so those are our goals. Those two are our mission from the beginning. And so Tess was patient eight, we're coming up on patient 200. [00:43:00] We're really close to that milestone. I remember we had this initiative when we were in the nineties of patients that was called Project Artemis, and Artemis is the Greek goddess of the hunt. And so the idea was we're hunting for patient 100, we're going to get to a hundred, please help us please share our podcasts and our social and all that and try to help us get to a hundred. So when we got to a hundred, it was this huge number, and now we're about to double that. So I'm really excited about that. But we've also been raising money for [00:43:30] years, and we're now at the point where we're able to fund some research, and that's exciting too.

Gina Mullane (43:36)
I'd love to hear about that. I understand you had a research grant award in '21. Could you tell us about the progress that's been made and what the research that you've been funding has been focused on?

Bo Bigelow (43:52):
Yeah, absolutely. So in 2021, we issued a two-year grant to an Austrian company called [00:44:00] Neurolentech, and it's a startup, and it was co-founded by this professor of neuroscience, Gaia Novarino at this Institute of Science and Technology in Austria, so IST Austria. So it's a hundred thousand bucks over two years, and they're basically going to be modeling Hao-Fountain syndrome in cells and just trying to understand a little bit more about how the mechanism of the disease works. We were talking about that before. And they're also going to use a mouse model to try to understand those mechanisms. [00:44:30] So that's a two-year grant. And unfortunately, COVID of course, has made it difficult to do basic things like even shipping samples and stuff. So we definitely have had some hiccups on that front, some just minor delays really relating to that project and trying to move things forward. So it is proceeding, but COVID has made it a little bit frustrating. It's difficult to try to do research during a pandemic.

Gina Mullane (44:59):
And do [00:45:00] you envision part of the research journey will involve collaborating with CROs to do some of that work for you? Bo Bigelow: 45:08 I think so. It's really important I think for us to figure out the best use of our funding because all of our funding has come from just families, grandmas and grandpas and aunts and uncles writing checks, and it's really, every penny has come from that. We don't have any kind of institutional funding. We don't have any investors or [00:45:30] anything like that. And so we have to be really careful about how we spend that money and how we can make it go the farthest. And so we have a grant process where we invite submissions and then we have a scientific advisory board that looks those over and tries to figure out which is the best, which is going to move things forward the most. And so now we're at the point, though, where we're starting to look at libraries and doing a screen and trying to figure out is there a small molecule?

We're not quite ready to get there yet. I think one thing that is a [00:46:00] complete head scratcher about this disease is that for many years we were certain that it was about a loss of function. In other words, you have USP7 not quite doing enough. And what we wanted to do, we thought was bump up expression of the gene to make it do more. And recently though, we're hearing about some patients who have too much expression of USP7. In other words, it's a gain of function for them and to get better, they need to knock down production of USP7. And [00:46:30] so if it's really both of those, that kind of changes things maybe for us, depending on how many people have a gain of function. But, I mean, we anticipate working with a CRO at some point, and we're always eager to have conversations I would say about what people are working on and how it might help us and how anything that they've already done might help us that's related. Because, like I said, those conversations are, that's how stuff happens.

Gina Mullane (46:58):
Yeah. So what does the [00:47:00] year ahead look like? You've clearly got a lot on your plate, very busy person with your many initiatives and your role as a patient advocate now and the work that your foundation is doing, what's ahead for Tess and all of that?

Bo Bigelow (47:20):
We are excited to begin the next piece of our journey with the foundation in that we are going to hire an executive [00:47:30] director. We haven't advertised for this position or anything yet, but that's sort of the next step. I've been filling that kind of role up to this point as chairman of the organization, but we're looking around and seeing other organizations that hire a full-time or part-time person, and were able to do a lot more. And I think with my other stuff, with my job as an attorney and everything, I think our organization [00:48:00] would be better served by having somebody in that role. And so we're pretty excited to have that, find the right person to have them come aboard and have them really supercharge our efforts and move forward, not just with the things we have in the works right now, but future collaborations.

They can have more of those conversations. We're part of an organization called COMBINEDBrain, which it's a consortium of nonprofits like ours that are all trying to cure neurodevelopmental disorders. And all the members of COMBINEDBrain have [00:48:30] a similar sort of profile. Nearly everyone I think is nonverbal and has some epilepsy component and has developmental disabilities, intellectual disability, I should say. And so that's a group of 30 organizations like ours, and we've just begun to tap into those connections. But if I had my way, I'd be talking to other COMBINEDBrain members every week, what are you guys doing for a registry and how's it going and how many people do you have and how can you drive more signups? [00:49:00] And we're in a biorepository through COMBINEDBrain and asking other people, what are people donating? How are you able to get more people to donate and what's your messaging about and all those things.

I think we should all be talking to each other about that because every time I do, even the limited amount I'm able to do, I learned so much from them. And that's what I think is so lovely about the rare disease community is that rather than kind of hiding all your work and not letting anybody peek at it, instead [00:49:30] people are opening up their trapper keeper and saying, look at my homework. Copy it. I'll make you a copy right now and send it to you. People are so willing to, if they've already solved the problem that you're contending with right now, they'll be upset if you go work on it and spend energy working on it because they've already solved it and they're like, just take my homework, copy it, cut and paste your foundation's name in my place, and you're off to the races. So [00:50:00] I really like that sharing. And so I think the COMBINEDBrain connection is the next big thing for us once we have an exec director on board.

Gina Mullane (50:10):
Yeah, very powerful. You've shared lots of inspiring messages here. What do you hope for your legacy?

Bo Bigelow (50:21):
One of the hardest things about this and about the glacial pace, I would say, of rare disease research is that [00:50:30] eventually you recognize that the cure or the treatment that you're working on is probably not going to be in time for your own child. I could be wrong. I hope I'm wrong. But my wife and I talk about it in terms of what if this isn't for Tess and for us? It doesn't make it matter any less. It doesn't make us work any less hard on it. It's just maybe a fact that Tess [00:51:00] might not get this cure and that it might come later and not be for her.

I think that is her legacy and ours is that it was during her lifetime that this disease became a thing and that it got a name and that we found all these patients and that we started the work to try to cure it. And with any luck, there'll be something, there'll be a small molecule or some other form of treatment or whatever, and it'll be for [00:51:30] the next generation. I don't know. It's hard to think about. It's a sad thing to think about to go that far into the future and think about it that way, but that's kind of how we look at it. I don't know.

Gina Mullane (51:41):
Yeah. Well, you're doing such great things. How can we help? What can our listeners do to help you get closer toward your goal?

Bo Bigelow (51:50):
The best thing, honestly, is to share our content. And I am not doing that from any perspective other than just finding more [00:52:00] patients. Our foundation has a bunch of social stuff that they're doing, sharing stuff about different people from all over the world, pictures of kids from all over, but their stories as well. A lot of parents are starting to write for our foundation's blog, just kind of telling their version of Hao-Fountain journey. I have my podcast, I have my blog. You can find me on social pretty easily. And just sharing what we have to say because [00:52:30] like I said before, that family's out there who's looking for us, and that family's 199 and 200. They're out there, and we're going to find them, and that's the best way for us to find them is if you share our stuff.

Gina Mullane (52:44):
Terrific. Well, we're on a mission to help, so we will do that for sure.

Bo Bigelow (52:47):
Thank you.

Gina Mullane (52:48):
I certainly feel not only inspired, but that I need to get to work here. Your industriousness makes me feel a little lazy. But thank you so much for [00:53:00] sharing all of that today and for spending some time with us today on Vital Science.

Bo Bigelow (53:06):
Thank you, Gina. Great to talk with you.

Todd Poley (53:10):
Bo Bigelow is the chairman and co-founder of the foundation for Hao-Fountain syndrome. You could find his Stronger Every Day blog and podcast at portlandrootsmedia.com. And listeners who are interested in tuning in to The Disorder Channel can find hours of free content by searching for [00:53:30] The Disorder Channel on Roku or Amazon Fire TV. Did you know that Charles River has a sister podcast? Eureka's Sounds of Science. This monthly podcast shares scientific, patient and advocacy perspectives on trending issues in the drug development industry. You can subscribe to Vital Science and Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Until then, thanks for listening.