A Mother’s Mission to Cure Rett Syndrome with Monica Coenraads

[00:00:03]Welcome to Get Real. There's much to learn about Rhett Syndrome and the research trust that you really got going here. I like to start with origin stories anyway and what got you here today before founding Rhett Syndrome Research Trust. You worked in the family business operating restaurants. What did that teach you about the grit required to be a founder? I often say that that's one of the best places to get that grit in a restaurant.

[00:00:30]>> The restaurant business is not easy.

[00:00:32][laughter] So my dad, who was an engineer, decided later in life to buy a restaurant. My mom, my brother, and I really tried to talk him out of it. We did not think it was a good idea. He knew nothing about running restaurants, but he did it anyway. And then he got sick. He needed a liver transplant. He was in a hospital away from home for about a year. I had just gotten an MBA.

[00:00:56]My brother had just gotten his bachelor's and we quit our jobs to kind of work at the restaurant, kind of rescue this restaurant that had no nobody to run it. We ended up spending 10 years there and we built it up over the years. It taught me a lot. It taught me, I think probably the most important thing is just self-confidence. It taught me how to manage people, how to manage customers, employees, scheduling, accounting, payroll, you know, you name it. I had my hands in everything. It was a small restaurant and you had to be an owner operator.

[00:01:28]>> Where was it? In Stamford, right?

[00:01:30]>> In Stamford, Connecticut. Yep.

[00:01:33]>> Is that where you are now? Where are you based now?

[00:01:35]>> No, I'm about half an hour from there.

[00:01:37]I'm in Trumble, Connecticut.

[00:01:38]>> All right. So, you're still in the same zone. Is the restaurant still going or how did that end? So, we sold it and the people that bought it ran it for a couple of years and then didn't do so well and then it's a Peruvian restaurant now.

[00:01:52]>> Interesting. What was your food like?

[00:01:54]>> It was a pasta restaurant. It was a diner when we bought it and then we changed uh we made all our own fresh pasta.

[00:02:01]>> Wow.

[00:02:02]>> From scratch and tons of specials every day. And yeah, it was a hopping place.

[00:02:08]>> Oh, that's cool.

[00:02:09]>> My brother's still in the restaurant business. He owns a restaurant in New Town. What's that called?

[00:02:14]>> It's called sal a pepe. Salt and pepper.

[00:02:16]>> Oh, it sounds great. I got to hit that.

[00:02:18]And is that how you know Barbara Palmer, our mutual friend from that part of the world or no?

[00:02:24]>> No, I know Barbara. We have a mutual friend, Rachel and Jason Rothschild.

[00:02:29]They're very close with Rachel. Rachel has a daughter with Rhett syndrome. She used to live in Stamford. I met her through the diagnosis of Rhett syndrome.

[00:02:37]>> And your daughter Chelsea has rat syndrome. What exactly is rat syndrome and when was it identified?

[00:02:44]>> So rat syndrome was initially well it's been around forever of course right before people knew it was rat syndrome.

[00:02:51]The first paper that came out about rat syndrome was written in the60s in a very obscure medical journal in German and not too many people read it. And then in the8s there was a paper written from another neurologist and that's when it started to become better known and people started getting diagnosed with rat syndrome based on a clinical presentation. So what your clinical history was and the symptoms that you presented. We didn't know the cause and then in 1999 the cause was identified.

[00:03:24]So mutations in a particular gene and that was discovered by a physician scientist in Houston called Huda Zagby and then we knew what the cause was and we had something to sink our teeth into and I think the research really took off from there from 1999.

[00:03:40]>> How old Chelsea? I mean you know when did you get >> Chelsea's turning 30 this year?

[00:03:46]>> Oh wow.

[00:03:46]>> Hard to believe. Yeah. She was diagnosed clinically at the age of two and then a year later in 99 the gene mutations were identified and she was one of the first kids to be tested and tested positive for a mutation in this gene. This is a gene that all of us have but if you have mutations in it leads to rat syndrome.

[00:04:08]>> Take us through the whole what was it like you know your 2-year-old kid I mean and then learning about this. We had the restaurant for 10 years and I was working crazy hours, 100 hours a week and it was very physical and we put off having kids until we sold the restaurant. Got pregnant right away and had a great pregnancy and she was the first grandchild on both sides of the family. So everybody was ecstatic and waiting impatiently for the birth. First year was pretty normal and then around a year I started becoming concerned. She wasn't learning new things. She wasn't pulling up to standing. She was not crawling. She had a funny way of crawling. She seemed disinterested in her environment. Things that she had learned how to do like wave bye-bye, play patty cake. She stopped doing. She started crossing her eyes. You know, she just seemed very autistic, stopped smiling, stopped looking at us. First we go to the pediatrician and then we went to a developmental pediatrician and then we went to a geneticist and then we went to a neurologist and every test we did came back normal through serendipity which you know often happens in life. I belonged to what back then in ' 989 was called a lister. So, I belonged to this email list of a bunch of other moms who would we had all had kids. October of 1996 and we were communicating with each other and are my kids doing this and my kids doing that and you know I had the kid that wasn't learning stuff. One of the moms reached out to me and said, "My next door neighbor has a daughter with rat syndrome. Look it up." So, I did. I looked it up and started doing this mental, you know, checking off. Yep. She does this, she does that. Oh my god. you know, I I think this might be it. Every doctor I spoke to saying, I think Chelsea has rat syndrome. They were like, no, it's so rare. I don't think so. I don't think so. But at the time, we were living in Virginia in Baltimore, there was a rat syndrome clinic. So, at Kennedy, John's Hopkins. So, we took her there.

[00:06:10]>> Wow.

[00:06:11]>> And they weren't used to seeing kids that young at the time. She was like 15, 16 months old. And we had to go back a couple of times. And then they gave her a diagnosis of Rhett. And then a few months later, the genetic cause was identified and we were able to do a blood test. At that point, her blood was in all the labs of the doctors that were trying to find the cause for Rhett syndrome. They got back to me immediately. And so it was devastating of course to kind of slowly realize over time >> right >> over a matter of say 6 months or so that our daughter was going to be severely disabled. Um and then I tried to turn that those emotions and really feeling helpless tried to say all right what can I do about it? At first it was like why us? Why me? Why her? And then it was like okay why why not us? let's try to do something about it. And that's what I've been doing ever since.

[00:07:09]>> And there really wasn't anything out there. You broke the ground. Chelsea really broke a lot of the ground.

[00:07:15]>> Up until that point, the effort had been to try to find the genetic cause of Rhett syndrome. And fortunately, that happened shortly after Chelsea was diagnosed clinically. So it was a great time to get involved. So yes, I mean there was nobody trying to develop a treatment or genetic medicine. The biotechs weren't interested. They had never heard of Rhett. It was an uphill battle.

[00:07:37]>> Well, you just had the blood test. You know, there'd be no way yet that anyone was going to jump on that. And then they really didn't. And we can get into that in a minute, but her primary caretaker.

[00:07:47]I'm also familiar with caretaking, but nothing like that. I mean, I had a wife with cancer and I've talked a lot about it. Let's hear what it's like caring for. I I mean I also have friends who have kids with rare diseases and I hear stories and we've had some people on the show here. What do you have to do? What are some of the things? Did you have to like build a new house or things in the house or all the things? I mean I'm sure >> yes we had to make some modifications to the house. So first of all, Chelsea is non-verbal.

[00:08:19]>> Okay.

[00:08:20]>> She does not walk. She could walk when she was younger with assistance. She never had balance. that you could hold her hands and she could take some steps.

[00:08:29]Over the years, she she's lost that ability. So, she can't stand. She can't help you like transfer weight or anything like that. So, completely unable to stand or assist in any kind of transfer. She cannot use her hands at all. So, she can't hold anything. She can't reach out for anything. She can't point. She is fed through a feeding tube. For many years, she had a feeding tube that fed into her stomach. We had to recently transition to a tube that feeds into her intestine because she was having lots of reflux. She has really bad seizures. They started at five. She So, she's been having seizures for 25 years. We tried medications and ketogenic diet. We've not been able to get them under control. She has orthopedic issues, scoliosis, and contractors and trouble sleeping and a host of other things. But a point I want to stress is that she's so much more than a laundry list of symptoms. She's got the most amazing personality. Even though communication is difficult, she's always smiling. She's patient. She's loving. She's affectionate. She's got a sense of humor. And we get her out every day. Wherever I go, she goes. And I do have a caregiver that comes 9 to5 during the week so that I can work. She comes to the house. Chelsea lives at home with us. You asked about modifications to the house. We turned our living room, which we really never used, was really large. We turned it into a bedroom and bathroom for her on the first floor. We have a ramp in the garage, and we have a wheelchair van.

[00:10:01]>> Okay. I was going to say, how you get her around? Yeah. So, I guess that's it.

[00:10:04]Yeah. I mean, you say she doesn't verbalize, but you're talking about all these wonderful traits. How does she express all that?

[00:10:12]>> She's very engaged. She has really good eye contact. You call her name, she looks at you right away.

[00:10:18]>> So, she's really there. I mean, it's not like you've lost her, right? I mean, it's not that kind of grief, right?

[00:10:24]>> No, she's there.

[00:10:25]>> I'm sure there's grief, but it's different.

[00:10:27]>> The grief changes over time. In the early days was like you'd been kicked in the stomach, like it physically hurt. A period of I don't know two or 3 weeks when I first realized how severe things were going to be where it was difficult to get up in the morning. You'd wake up, you'd be okay for two seconds, then you'd remember, and then it was like a crushing feeling on your chest, like just crushing. You know, you can't exist and keep going with that kind of emotion. So, it does get better and but it still hits you at times. You her school friends that she's had over the years going to college and getting married and having careers and her brothers moving on with their lives.

[00:11:11]It's always a little bittersweet.

[00:11:12]>> Yeah. And they don't have this any trace of it. Nothing.

[00:11:17]>> No. For the majority of cases, it does not run in families. It's a sporadic mutation that happens. And the vast majority of families have never heard of Rhett syndrome, and it doesn't run in their family. There's a few rare, unusual cases of familial Rhett syndrome. And then if Chelsea was to have a baby, she'd have a 50% chance of passing it on. But kids with Rhett syndrome don't have kids. So it stops there. If we cured it and these kids would go on to have children, you could do pre-implantation testing to make sure that you're in you do in vitro when you implant an embryo that doesn't have the mutation. So there'd be a way around it, >> right? So you've channeled that feeling.

[00:12:00]I feel it just talking to you about it.

[00:12:03]You know, I I just feel it. you've channeled that into launching and building an organization that is designed to tackle clinical trials and treatment. So, how has it gone? Where are we? I mean, and what's the journey been like?

[00:12:16]>> Yeah. So, in the beginning, it was really focused on basic science, right?

[00:12:21]We didn't know much about this gene, what does it do? Where is it in the body? What does the protein do? How do the mutations affect the protein?

[00:12:28]>> And how did it even get triggered? She was fine for a year, right? Or we weren't sure. Well, yes. That's because when a baby's born, there's very low levels of this protein. It's not really needed. As a baby matures and becomes a toddler, the amount of protein in the brain gets just naturally you get more and more of it as it's needed and it's involved for more. It's involved with, you know, learning and more advanced skills and when it's needed and it's mutated and not doing its job, then the problems show up.

[00:12:59]>> Got it. But so in the beginning I would say the first you know seven or eight years we tried to get academic researchers interested in the disorder.

[00:13:11]So we were raising money and we were giving out smaller grants say $50,000 a year for two or three years to lots of different labs trying >> Was that at John's Hopkins mostly because you said they had a clinic.

[00:13:24]>> No. So we weren't really funding clinicians. we were funding basic scientists, molecular geneticists, neurobiologists and so it was more PhDs not MDs um in the be just trying to understand the function what does this protein do and where does it where does it live and we did that for a number of years and then there was a landmark paper that we funded that really kind of changed everything and this was a paper that was came out of the lab of Adrien bird at the University of Edinburgh in Scotland and he did an experiment where he genetically engineered these mice models so that they were missing the gene that's mutated in Rhett syndrome and they developed Rhett symptoms as much as a mouse can have rat symptoms.

[00:14:16]But then they were able to modify this gene that was kept. It's not that it didn't have the gene, but the gene was modified so that it wouldn't make the protein, but then it will by doing something else. We don't have to get into the details. You can turn the gene back on and then the gene starts to make its protein. And the question he was trying to answer is if we can restore levels of the protein. So genes make proteins. If you have a mutated gene, you're going to have a mutated protein.

[00:14:47]So the question was, if we turn this gene back on and it starts to make normal protein, what happens to the symptoms? Is it reversible? Are they reversible? Is there a window of opportunity within which you have to act? Or can you take an old mouse that's never had the protein, turn it back on, turn the gene back on, it makes the protein and the symptoms go away. So that's what he was trying to answer. And the unexpected answer was that the symptoms are all reversible. complete almost completely reversible and the age didn't matter. You could do it in a young mouse, an old mouse, the symptoms go away. And the other thing he did was you can take a normal adult mouse and take the protein away and that mouse develops rat symptoms >> and you can't synthetically, you know, because obviously a lot of our world is based on protein drugs that replace or replenish that which you don't produce or you lose. Is that one of the approaches or do you have to turn the gene back on?

[00:15:48]>> We are advancing a number of genetic medicines. So after that paper came out, it really changed the focus of what I wanted to do. At that point, I was like, right, we're going full-on genetic medicines, not small molecule drugs, because this is a complicated gene that does a lot of things. And a drug may act on one pathway, but you know, you're leaving a bunch of other pathways untouched. So let's go after the root cause of the disease. The one genetic medicine modality that everybody's familiar with is gene therapy, right?

[00:16:19]You're basically supplementing a gene to compensate for a mutated gene. So we started funding gene therapy and then as new technologies were discovered like for example base editing, you can now fix a particular kind of mutation or RNA RNA transplanting. As these new technologies became available, we added them to our portfolio. So, we're now advancing a number of modalities, some of which should work for all mutations, some of the modalities work for only some of the mutations. We're constantly, you know, looking at the science and making decisions about what do we advance, what do we prune, what new things are there. And there's two gene therapy trials now that are underway.

[00:17:03]These were gene therapy programs that started at the Rhett Syndrome Research Trust. We funded these investigators for years and years and years. They generated the data that got these companies intrigued. They licensed the programs and now they're advancing them.

[00:17:17]So, we have two gene therapy trials ongoing and then we're advancing a number of other modalities.

[00:17:23]>> How do you raise money? How did you get people interested to help you raise the money you needed to get all this going?

[00:17:28]How much does it cost? I know what it takes to bring a drug to market. It's like crazy.

[00:17:34]>> It is crazy. We don't have to raise all the money. Well, first of all, to answer your first question, our money comes from efforts of families like mine that have a child with Rhett syndrome.

[00:17:45]>> How many is that approximately, do you think?

[00:17:48]>> 15,000 in the US. Only a small number actually fund raise. Unfortunately, that's the case for disease. It's always a small subset of people. So those families donate personally and importantly reach out to their networks.

[00:18:02]So we've been raising somewhere between 7 and $9 million a year.

[00:18:06]>> That's incredible. Yeah.

[00:18:07]>> And we've raised I think the latest number was like 120 million since I started. And we don't have to raise all the money to get something commercialized. We have to raise enough to generate the preliminary data to then get a biotech company interested and then they move it ahead with their own money.

[00:18:26]>> So we've got some biotechs involved now.

[00:18:28]>> Yeah, there's actually quite a few involved. Two gene therapy companies that have clinical trials. There's other companies that are in the gene therapy space that haven't yet gone public with their programs. There's RNA editing companies. So there we're not acting on the gene, but we're actually trying to fix the RNA. There's a company that we're funding in the Netherlands called Procure and there's a couple of other companies here in the US. The difference is if you have a common disease like Alzheimer's or something that's very wellnown, companies are going to pursue those on their own. For a rare disease, companies are not going to start from scratch their programs for rare diseases. So they really have to count on an organization like ours to generate the preliminary data, get that data going, get those programs going, and then put it on a silver platter and say, "Here, are you interested?" But they're not going to start from scratch. So that's the difference.

[00:19:27]>> No, I know we've had Kathy Juicy on to talk about multiple myoma foundation.

[00:19:32]I've been involved with the Leukemia and Lymphoma Foundation. And back in the day when I was at Janentech with a lot of the growth hormone and growth disorders as well as I mean there's the list goes on and on as you know. Do you ever feel like a hero or I mean it's kind of amazing what you're doing.

[00:19:51]>> No quite the opposite. I'm reminded every single day that despite the funds raised and all the efforts and I'm a workaholic, so a lot of work over the past 27 years, my daughter has absolutely nothing to show for it yet.

[00:20:08]And neither does any other child with Rhett.

[00:20:11]>> She knows you're at it though somehow, doesn't she?

[00:20:13]>> Yes, she absolutely does. and it's the only reason that I'm able to look her in the eye every day. Once she has something to show for it and other individuals as well, then we'll take a step back and say, "Okay, job well done." But we're not there yet.

[00:20:28]>> But qualifying as a rare disease, just you mentioned the big diseases. What is that? Just remind us that you can develop treatments under that umbrella.

[00:20:36]I mean, do we still have all the special rules that I remember we were able to create out of Janentech?

[00:20:42]>> Yeah, there are some. And the definition of a rare disease is that it needs to affect under 200,000 people in the US.

[00:20:49]So we're definitely a rare disease. In the world of rare diseases, we're a fairly common one actually because there's ultra rare and that's even tougher, >> right? Yeah. There's been a lot of protesting and marches on DC. I saw one, you know, at the FDA. Well, there were two in a row. Are you guys part of that activism or not? No, we're a small organization with limited bandwidth and we just focus on what we think we do best. There's other people out there that do lobbying and we don't. So, we leave that up to others that can do it better than we do. That's not our field.

[00:21:27]>> And you partner with them, right? I mean, what else can you do? I mean, are there a bunch of orgs or like there's not that many. It's a handful, right?

[00:21:34]Focused on Rhett.

[00:21:35]>> Oh, focused on Rhett. There's a couple and then of course there's every like in Europe for example every country has at least one some have four or five but we're the only ones that are focused on genetic medicines.

[00:21:47]>> So yeah let's talk about that. What's the state of gene therapy? That seems to be the forret syndrome that is that the furthest along in the things that you're looking at.

[00:21:57]>> That's the furthest along. It's the only genetic medicine that is in clinical trials. The things that we're advancing are still in the lab. haven't moved to clinical trials yet. So, there's two companies and they've both are in what's called pivotal trials or registrational trials. They fully enrolled trials where the FDA is expected to be able to make a decision on approval or not. Companies are sharing some information on efficacy, but more information shared during the year. With something like Rhett syndrome, you're not going to get an immediate, you know, you have gene therapy today and tomorrow you're better. It's going to take some time.

[00:22:34]And what we still don't know is there may be some modest improvements in year one. Will there be more improvements in year two? Will they continue to build?

[00:22:44]And maybe five years out you've got dramatic improvements. You know, we don't know that yet. But you can imagine not, you know, having all these symptoms and not having had the possibility to speak and maybe the seizures are so bad you missed a ton of school and all these other things. is like that's going to take time to really learn skills. So I think it's still early days.

[00:23:04]>> Well, this leads to a whole ton of other questions. If we do get good signs that it's helpful in that short term and then but you have to stay on it, keep getting more and more benefit. It's not a oneanddone treatment, is it? Or it is and then you watch and see what happens, right?

[00:23:23]>> Yep. It's a oneandone. And the other thing to mention because it's very critical for families and so gene therapy or gene supplementation, right, where you're adding healthy genes into the body that has to be delivered.

[00:23:37]That's the cargo, right? The gene is the cargo and then you need delivery vehicle. And the delivery vehicle in most cases is a virus. You can only get a virus one time because basically you're inoculate against it. So if you give it again, you're going to have a very bad immune response that could kill you. So you can only get gene therapy delivered with the virus one time. And so drug development and genetic medicine also, it's an iterative process. The first gene therapy that's going to be approved is unlikely to be the last or the best. It's the first step. There may be other better gene therapies that come along, but if they're delivered virally and you've already had the first one, you're not going to be to get the other one. So, this is something that is tough for families to figure out. Do I jump in now into a trial or when it's commercialized, do I wait for something better? Yeah, tough decisions.

[00:24:34]>> How many patients are in the trials?

[00:24:36]>> The trials are small. They've been like 15 people, something like that. So, the trials are small. Gene therapy trials are always small. It's very expensive to make gene therapies and they're always small. So once it's commercialized, yeah, families and we're assuming they'll be commercialized and families will have to make that decision.

[00:24:55]>> Well, that's the question. So, you know, you mentioned it's very expensive.

[00:24:59]What's the cost per patient for treatment and how much does obviously insurance does not cover this now?

[00:25:06]>> Other gene therapies that for other diseases insurance does cover it >> does cover but not yet. Not for rats.

[00:25:13]>> No, but there's nothing commercialized yet. So, I'm sure the companies, they're going to assume that they're going to get commercialized. And so, I'm sure efforts are underway where they're already talking to insurance companies and Medicaid, Medicare, mostly Medicaid, but to get it covered because these are going to be multi-million dollar therapeutics. And there is no business model if patients have to pay because how many patients would be able to afford, I don't know, $2 to4 million?

[00:25:41]Not many.

[00:25:41]>> But would you start raising money for that then? I guess probably to some degree, but then that would be hard.

[00:25:47]>> Well, I don't think we could raise enough to cover everybody. It really needs to be the companies need to be contracting and coming to agreements with insurance companies and and Medicaid to to cover it. So for example, spinal muscular atrophy has a gene therapy called Jensen and it's available in I don't know 50 countries or more by now and either governments pay if they're socialized medicine or private insurance or Medicaid pays in the US and that's been the case for quite a number of years now. So it can be done for something that's transformative, >> right? I mean that's the key, right? you you made that point that you won't know maybe for a few years how transformative, but we always make the argument that we're saving costs of these 15,000 patients in other ways and that for an insurer could be very helpful because I imagine you're you're tapping insurance to keep Chelsea where she needs to be.

[00:26:50]>> Yeah. And it's not just medical costs.

[00:26:52]So, I mean, for a lot of these kids, Medicaid is paying for help in the house or to modify the house or feeding tubes.

[00:27:00]And the formula, Chelsea's formula alone is $1,200 a month, medications, and hospitalizations. They often have to have surgeries and they often get pneumonia and then so but how to pay for these very expensive medications is a whole other topic that really I'm not an expert on it but people have to figure this out because when there's only a handful of gene therapies any insure payer is only going to have a few individuals in their policies right but when you've got a hundred gene therapies and there's going to be more and more and more every here, they're going to start bulking. Well, we can't afford it.

[00:27:40]So, there needs to be the economics of it and the business model. People are going to have to figure out because what a shame it would be if we have transformative treatments and we just can't figure out how to pay for them.

[00:27:50]That that would be an incredible tragedy.

[00:27:53]>> Well, that's a conundrum, but obviously if it's a cure, you know, the better it works, the better chance, right? because if you get what you pay for in that I think that example you gave before is a good one because there's real advance you know you really see change and difference and I mean some of the gene therapies are delivering incremental change that's a little harder potentially to justify than completely getting somebody back into life >> and in time there are drugs that are out there for example for musculardrophe that nobody really knows if they work or not. And yet they're out there and payers are paying for it. But eventually something better will come along. And when something better comes along, everybody will know it. And then no one's going to go after the drugs that are incremental, >> right? We have to do it as a society. We have to allow it or we'll never get there. Now we completely accept GLP1s, but for many, many years that was not ubiquitous. And then we started with a very high cost and now it's low and that's true for Rapatha which lowers your cholesterol dramatically. I mean I think we're going to see it. You're at the cutting edge. I mean with limited resources and a smaller team. How do you decide what to push forward? Obviously you have to decide I'm going to worry about that payment thing later. Right now I need to worry about getting this thing to work.

[00:29:20]>> Yes. And you've kind of nailed what my philosophy has always been like. like we're going to tackle one big problem at a time and we're not going to look down the road at 10 steps from now what that big problem's going to be. Well, for one thing, we've decided to focus on genetic medicines. It was a thoughtful decision to say we're not going to go after small molecule drugs. Like we can't do everything. We're also not a family support organization. We're not an awareness organization. We're research and we're focused on solely on genetic medicines. That decision was made so that we can have the bandwidth that we need to really focus on what we do best.

[00:29:52]And then everything else is data driven.

[00:29:54]Kind of data driven. These projects start off. We don't take on a project that's going to be $20 million right off the bat. We'll start off with a project that needs 2 million to get it going.

[00:30:04]And then we see what happens with the data. We generate the data and does it look good and not? We prune things.

[00:30:10]We've stopped projects. And then for example with base editing or RNA editing if it turns out that an approach that works for all mutations gives us the kind of results that we need well then we don't need a base editing or an RNA editing you know and then we'll prune those. So it's always kind of looking at what you have and figuring out what are the go no go decisions and it's iterative.

[00:30:31]>> Does AI help us? I mean everybody says AI is the great savior. Is that going to be good that we have these new techs to help?

[00:30:39]>> Yes. The companies that we work with are some of them are definitely using AI. So for example with one of our base editing projects we've partnered with an AI company called Proffluent who uses AI to develop editors that are small and can fit into the cargo space that we have available to us with a vir viral delivery. For example, there are companies that are using AI to engineer viruses so that they can get into the brain better. You know, they're using AI for all sorts of things.

[00:31:15]>> And are you collaborating with some of the ones who have been successful in getting these gene therapies to market?

[00:31:22]I mean, you're learning from it, of course, but are you collaborating with some of those companies and and scientists and people?

[00:31:29]>> I wouldn't call it so much as collaborating as as lessons learned.

[00:31:33]What can we learn from that? But honestly, there haven't been that many gene therapies of the kind that we need that sensma is one of them, the SMA. So, there's been a lot of lessons learned there.

[00:31:46]>> That gives you hope. How do you feel?

[00:31:47]Where are we? Are you feeling optimistic? I guess you have to.

[00:31:51]>> You can't be in this line of work if you're not optimistic. Like, yes, I'm an eternal optimist. And the more I learn, the more optimistic I am. I hope that when we have something that's transformative that Chelsea can still benefit from it and I've met so many families over the years and I'm motivated by their kids as well and but yes, I'm very optimistic.

[00:32:13]>> Does life ever feel normal?

[00:32:15]>> I have a pretty abnormal life. I would say life with Chelsea is I mean compared to lots of other people, it's not normal. We can't travel with her. We don't go on vacations cuz I won't leave her home. We can't really be spontaneous. It's difficult to be spontaneous. She has seizures often like wherever we go. So, we have to be able to like I wouldn't go out on a boat with her because what if she has a really bad seizure and I need to get her to a hospital or something like that. So, we're careful about what we do. We always kind of have an exit strategy. If we're going somewhere where my husband or I, one of us has to stay, we might go with two cars. That kind of thing. And then I guess the other reason life is not normal is more of a decision on my part, but I pretty much work 7 days a week.

[00:32:59]>> Have you ever left her?

[00:33:01]>> Occasionally for work, very short one, two, three day trips. Very, very short.

[00:33:05]That's it.

[00:33:06]>> And your husband or the caregiver or somebody watches her?

[00:33:10]>> It really takes two people to lift Chelsea now. So I can't leave her with one person. I have to leave her with two people. So if I'm have to go somewhere then my husband has to be here um to be with the caregiver.

[00:33:22]>> How'd you handle the boy's graduation and all that stuff you know?

[00:33:26]>> Well my older son graduated during COVID so there was no graduation. So that took care of that.

[00:33:32]>> All right. That was the one silver lining of co I guess. So >> my other son he was in New Hampshire and we took her uh with our van. My husband came up with a very cool idea. We have a wheelchair van, a ramp off the back, and two captain chairs or whatever you call them behind the driver and passenger and she fits in the middle with her wheelchair. So, he came up with this idea of we can take the wheelchair out.

[00:33:58]We have a piece of plywood and a crib mattress that we lay on top of the two chairs. We can lift her. He lifts her, walks her in, lays her down. We can change her, let her stretch. So, you know, if we're driving a long distance, we stop somewhere and get her out and change her and let her stretch and let her take a nap, whatever. And then we'll just pick up and keep going. So, we do that.

[00:34:22]>> Great. I mean, I guess that's sort of a vacation or not really.

[00:34:26]>> You know, at home, we have all of the comforts that make it easier to take care of. We need to bring a lot of stuff with us, [laughter] >> right? So, there's an album that's a soundtrack to your life. What is that?

[00:34:37]>> Oh god, I don't know. I'd have to think about that.

[00:34:40]>> Does she respond to music?

[00:34:42]>> Yes, she loves music and she listens to a lot of 70s music because that's what I like. But when her brothers are here, she'll listen to other She'll listen to anything. She's very easygoing. She does love music.

[00:34:54]>> Do you see a different response in her when that's happening?

[00:34:57]>> Yeah. Pays attention and she perks up and Yeah.

[00:35:01]>> That's great. Yeah. I mean, I'm working on a program. I'm going to I we just are about to launch a podcast about music and the mind and music and medicine and how important that is in all kinds of diseases, but I would imagine in these sort of rare diseases even more so in some ways because it really engages you.

[00:35:22]>> And I know there's studies on if you listen to music when you're having like painful procedures done or anxietyprovoking procedures that can help. So, >> what's something that you're getting real about right now besides what we just got real about?

[00:35:39]>> Trying to carve out some me time. I'm bad at that.

[00:35:43]>> Yeah, sounds like you you could use that.

[00:35:46]>> Yeah. So, trying to get real about starting to work out and just a little little me time. Not sure if I'll be successful.

[00:35:54]>> Well, do do you think that would be good for her? I mean, you dedicated a lot of your life to her. Somehow you've managed to raise two other boys that sound pretty normal and healthy. Do they have Are they all for it or is there resentment? I mean, is there any They're all in.

[00:36:09]>> Oh, no. No resentment. They love her to pieces and Yeah. No. No.

[00:36:14]>> Yeah. And just have helped and supported in the cause. They're all part of it.

[00:36:18]Did anyone come into the family business? Are they in it? I mean, are they in the foundation in the trust?

[00:36:24]>> We're not big enough for that. Like, we're >> How big? Yeah. How many people are involved?

[00:36:29]>> So, besides myself, we have four people on our research team. We have a somebody with decades of uh genetic medicine background. We have someone that has deep deep experience in Rhett syndrome that worked in a RET lab. We've got a chief medical officer. We have kind of a a research manager, chief development officer, and an administrative officer.

[00:36:50]And then we have some part-time folks or some contractors. So, you know, we're under 10 people. Yeah, we're lean. Yeah, you run lean and mean. For my audience, let's ask this question and see what you say. What do you need from us? What do you need from us, the community, from everyone to move this to the next phase and step?

[00:37:09]>> If anyone listens to this and is moved to make a donation, of course, we would love that. You could Google Rhett Syndrome Research Trust. If you know somebody that has Rhett Syndrome, let them know about our organization. I mean really awareness is always important and maybe people know somebody that sits on a foundation that funds whether it's women's disorders or you know children diseases or maybe they have a philanthropic family member, maybe they want to volunteer some time, maybe they whatever it is, we're only an email away.

[00:37:43]>> Is there anything everybody needs to know about Rhett syndrome? Do you think they're misunderstanding? Well, I mean, one thing that doesn't just apply to Rhett, applies to everyone that's kind of non-verbal. Just because they can't speak doesn't mean they have nothing to say. And it doesn't mean that they can't understand what you're saying. So, I'm always disappointed when we talk to people and they ignore Chelsea. It's like, say hello, say something. She's 30 years old. She's not a child.

[00:38:11]Acknowledge her. I would say acknowledge people whether they can speak or not. A lot of people do and it's wonderful when they do, but a lot of people don't. They don't think of it or they feel awkward.

[00:38:20]They don't know what to say. And so it's just easier to ignore.

[00:38:24]>> Yeah.

[00:38:24]>> But that always hurts a little bit. And I don't know what she thinks about it.

[00:38:28]But it doesn't take much to just say hello and comment about something. I love your hair. It's great what you're wearing. Or what a cool wheelchair.

[00:38:37]Something, you know, say something.

[00:38:38]>> Look what she made happen. She made her mom do this, leaving pasta making to drug making and possibly changing the world in a big way. So that that's huge.

[00:38:53]>> Yeah. I tell her that without ever saying a word, she's had a big impact and I hope a bigger impact to come.

[00:39:00]>> You're changing the world and that we just want to say thanks and our audience, you know, hopefully will get more active and involved as a result.

[00:39:09]Well, thank you, Jim. I appreciate that.

[00:39:11]>> Great to finally meet you and we'll be sharing this far and wide. As far as wide as I can get it.

[00:39:17]>> Awesome. I appreciate that. Thank you.

[00:39:19]>> Thanks for being here.

[00:39:22]Hey everyone, thanks for watching. I really appreciate that you take the time to listen to this and tune in. So, please [music] subscribe, follow. I've got a lot of amazing guests. You're going to learn a lot and you're going to feel a lot better because you [music] did