Episode 3: Inside OCNDS Research ft. Drs. Gabrielle Rushing and Elena Bagatelas

In Episode 3 of Roadmap to Rare, host Eric Finn is joined by Dr. Gabrielle Rushing, Chief Scientific Officer for the CSNK2A1 Foundation, and Dr. Elena Bagatelas. Together, they unpack the science behind Okur-Chung Neurodevelopmental Syndrome (OCNDS), from explaining the functions of the CNSK2A1 gene and the CK2 protein, to talking about the foundation’s genotype (genetic code)-phenotype (physical result) research, patient registries, and current research priorities. The researchers highlight that every family’s participation helps move research forward. 

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Links & Resources:

https://www.simonssearchlight.org/research/what-we-study/csnk2a1/

https://www.csnk2a1foundation.org/simons-searchlight

https://www.csnk2a1foundation.org/citizen-health

https://www.csnk2a1foundation.org/project-find-out

https://www.csnk2a1foundation.org/new-partnership-with-probably-genetic

Bagatelas et al., 2025. OCNDS core features are conserved across variants with loop-region mutations driving greater symptom burden: https://pmc.ncbi.nlm.nih.gov/articles/PMC12267189/

Transcript

Speaker 2 0:07

Hello everybody and thank you for joining this episode of Roadmap to Rare, our podcast where we discuss the reality of the rare disease journey through real stories, real challenges, and research. Today I'm joined by our two esteemed doctors. Um, first, uh Dr. Gabrielle Rushing. She's our Chief Scientific Officer for the CSNK2A1 Foundation, and Dr. Elena Begatellis. Thank you guys for joining me.

Speaker 0:34

Thank you. Gabrielle, do you want to introduce yourself first?

Speaker 1 0:39

Sure. Yeah, hi everyone. Uh, so I am the chief scientific officer, as Eric mentioned. I originally started at the foundation approximately three years ago. Time has been flying. And I started as the inaugural science director at the foundation. Um, I joined from a former rare disease patient advocacy organization called the TSC Alliance, and they were much larger. They now have a team, I think, of 30. It was close to that when I left. So I uh definitely switched gears coming into this very small foundation, and I remain the only full-time paid employee. Um, but it's been really, really exciting working with Jennifer in what we call a uh startup mode to work with the foundation. Um, and prior to working at the TSC Alliance, I did my PhD specializing in neuroscience at Vanderbilt University, and I studied TSC, which is um tuberous sclerosis complex, another complicated name for a rare disorder, um, during my graduate work. And that's how I segued really into rare disease. I found it quite fascinating studying all these lingering questions and wondering why can't we find treatments for these people? It should be straightforward, right? Um, and soon I learned just how complex things can be. So really excited to be here and talk to you guys about all the great work that's been going on.

Speaker 2:00

Great. And briefly, I'm Elena Bagatelas, as Eric mentioned. I had the incredible opportunity of being linked up with the foundation during my time as a postdoctor or a doctoral graduate student, also pursuing my PhD in neuroscience at Vanderbilt. And during my time, I was able to intern with the CSNK2A1 Foundation and had just an incredibly fruitful time where we got to publish work on the phenotype-genotype relationship of Okur Chung syndrome, which we will touch on today, and also just you know bred a relationship that's been fostered ever since. And I've had the incredible opportunity to work with Eric and really developing this podcast and getting boots on the ground. So thanks for having me as a special co-host episode on today's episode, Eric.

Speaker 2 2:51

Absolutely. And it's not too rare, but it's very to have two people with doctors, way more schooling than I've ever had myself on an episode. So, Dr. Rushing, I know our listeners have heard me use Okur Chung Neurodevelopmental Syndrome or OCNDS as uh the syndrome that my son has. Um today we're gonna kind of dive into the other side of it, the CSNK2A1 um foundation that works with OCNDS. Um, how how does that work on your end?

Speaker 1 3:23

Yeah, and that's a great question, Eric. So it's it is quite complicated with all of the different names. So CSNK2A1 is the gene name, and this gene is what is affected in the DNA that then causes OCNDS to happen. The reason OCNDS has its name is because back in 2016, so almost 10 years ago, when this was first discovered, the leading uh geneticists that determined that this gene was causative for a rare neurodevelopmental disorder were Dr. Volkan Okur and Dr. Wendy Chung, and hence it's a very common strategy when we have a new disorder to name it with doctors' names. And then over time, what eventually tends to happen is as we learn more, things will get renamed appropriately. And so CSNK2A1 is the gene. The protein that is made is also a different name called CK2 or casein kinase 2. And what we've learned over the years, since it was studied in isolation outside of even knowing OCNDS existed, it's a critical protein in our bodies, meaning it's critical for life. If you don't have any of it, organisms do not survive. And it's well conserved across species, meaning it's present in flies, you know, those annoying fruit flies that happen in your kitchen, fish, mice, anything you can think of. This kind of so important. Yes, tadpoles, frogs, exactly. It is so critical that we can use multiple model species to study it. Um, and it's called a kinase. That's the type of protein it is. But that's the connection between CSNK2A1 and then OCNDS naming. Perfect.

Speaker 2 5:07

I've always kind of wondered that. Uh so Dr. Rushing, uh, would you mind giving your elevator pitch of your role within the foundation?

Speaker 1 5:17

Oh, yes. Um, so as Chief Scientific Officer here and the only full-time employee, I do wear quite a few hats at work and do maybe some things that a traditional chief scientific officer at a larger organization wouldn't do. But broadly, I am driving our scientific strategy, um, helping to find the right people at the right places that can help us answer key remaining gaps in the field, because every new answer then gives us insights into what we need to do next. And so I do like to say a negative result or negative finding isn't necessarily a negative thing, so to speak. It just tells us, okay, we need to shift direction here. And as part of that infrastructure, we are conducting our own research at the foundation. And so Elena being here is really, really lovely. Um, I initiated an internship program when I first joined the foundation for multiple reasons. One, I was an intern formally at TSC Alliance during my grad program, and I got exposure to this being an actual career. Traditionally, when you go into a PhD program, you're told you can stay in academia, so at a school, running your own lab, so to speak, or you can go into what's broadly defined as industry. So think of like big pharmaceutical companies, drug development, bigger, bigger corporations. Um, but recently uh there's been a lot more exposure into what's called an alternative career, and this is this is one of them, um, taking what you've learned in your graduate program and broadly applying it to help answer questions. And so, as part of that, when I initiated the internship program, it was really, really helpful for me in two ways. One, I got mostly free help or very reduced rate help from very smart, motivated people that wanted to help make a difference and get exposure to nonprofit. And then two, I was able to have mentorship opportunities that I otherwise would not have had, being the only full-time employee here. Um so as part of that, we've been able to do a lot more projects than I would have been able to do solo, one of which was with Elena leading a project on what we call genotype, phenotype analyses. And I know that's a mouthful, so I'll break that down briefly. So, genotype is the change in the DNA that we're talking about. So if we think about OCNDS, we're talking about changes in the CSNK2A1 gene. And so that's genotype, it's whatever change you have in the DNA. Phenotype is what I describe as the outward appearance or manifestation of that genetic change. And so we can think of OCNDS and the symptoms that present. It gets a little tricky, as Eric, you probably know, because individuals with OCNDS have such varying symptoms as well as symptom severity. And so when we say genotype-phenotype correlations, what we're trying to see is if people who have the same genetic change do they have the same symptom presentation or severity? Can we predict maybe what symptoms might present in specific people by a certain age range and so forth? Lots of complicated layered questions. But as we start finding more people over time, we can start diving in and hopefully answering those questions more broadly. But it's a little side tangent, but um, yeah, broadly we're doing science strategy and trying to find a treatment for people and families affected by OCNDS.

Speaker 2 8:52

Um, so Dr. Rushing, uh Dr. Bagatelas, I know we've been talking about the genotypes, phenotypes, all that kind of stuff. And I remember from our uh the the big conference that we had with all the different OCNDS families in one place, and I remember one slideshow, one slide from the slideshow had like a hundred and some odd 200 different variants um with that specific CSNK is the CSNK2A1 gene, but there's so many, and all of a sudden you had like so many cases by color and stuff, and it was just fascinating to see like, oh, okay, well, I think my son Ronan is is in this one. Good. I had the the report on my phone. Okay. Let's go through the report. Okay, it said we're here. Okay. Alright, there's five five kids or five people with that. Okay. And then kind of it was just fascinating that the rest of it that went through. So um, if you don't mind, um if one of you or both of you hopefully um could talk a little bit more about I call them characteristics, and I know it's probably different than you know, like kind of how it manifests itself, but like characteristics are like how it how of course or you know, as you're like reading a book, like, oh, this guy had a characteristic of being this, so you maybe not you see it or you read it, that kind of thing. So you guys wouldn't mind talking a little bit more about those.

Speaker 10:14

Yeah, I can take a first jab at it, and Gabrielle, we can expand on it together. But first off, I really liked your photographic memory, Eric, because I actually remember you approaching me at that conference with your sun genetic report and just asking really relevant, yeah, really relevant and really good questions that I think is just really cool to see a parent be able to distill down scientific information in a way and try to apply it to their present situation in their family case study. So, to your point of also distilling down the word phenotype to characteristics, that's exactly really what our goal was. So we were aiming to, with the Simon Searchlights data, which is a database where any new families that they haven't already submitted or added their names to that registry, they can participate because that is a huge added bonus for us basic researchers, be able to really learn more and expand on what we still don't know about OCNDS. But with the Simon Searchlight database, we are able to extract relevant information of not only information about the individuals with OCNDS, but also their siblings and parents. And this registry or collection of data can really include anything ranging from behavioral analysis that the clinician can perform, whether it's on sleep or medications that are prescriptive or non-prescriptive that are being taken by the individual. It also can have what we call longitudinal data or really data where they can track a time point in the participants regarding sleep or physical examinations and then follow the trajectory from a follow-up examination, say, for example, a year after, two years after, and so forth. And so, with this, you know, abundance of information, it can really allow us to extrapolate or dissect out information that we can then piece together in a way to kind of put some puzzle pieces that could inform maybe a little more about how this disorder manifests, depending on where an individual may harbor a mutation. And so, what do I mean by that? So, case in point of really what our phenotype, genotype analysis was was like you mentioned, Eric, we have the gene. And if you imagine we have the full-length, you know, form of the gene, we can have individual points along this gene where there can be mutations. Now, if this were then to result in a protein where the gene encodes the protein that is expressed or readily available in the human body of these individuals, that protein is then going to have a mutation. And so where those individual mutations are located, we're able to exactly locate and then kind of do a binning or grouping where we can group them exactly like you saw. And so I think the figure you're referencing that you saw was where we had mutations grouped according to whether they were in what are conserved loop regions. So a region of the protein that has been well defined across literature, where these regions are really important for interactions with other proteins in the body or really important for that protein's function as a whole. And then we were able to compare that to another group that we defined as non-loop regions. But really, what I just want you to take away from hearing those two different terms is that we were able to group them according to two different groups, and we then were able to really try to dissect out whether there were any changes in, for example, um phenotype such as hypotonia or low muscle tone. And so that was one of the phenotypes we were able to observe as a difference between the two groups. We also were able, or maybe I should say not able, because this disorder, as Gabrielle pointed out, is quite new and is considered an ultra-rare disorder or a rare disorder. There is not quite a severity scale associated with this disorder that we know of to date. So that's just due, once again, to the fact that there are not enough individuals with this disorder that have been seen and diagnosed. And so to be able to follow the prognosis of this disorder with a specific severity scale, we need more information. And so in our research, we kind of came up with one that is pretty relevant to the way other groups would define severity, where we are able to collectively look at the number of symptoms an individual has, and then we use that as an informative tool to inform the severity or the phenotype severity that an individual has.

Speaker 1 15:00

And so sort of as a proxy for it. Sure.

Speaker 2 15:07

I mean, you're you're you're taking you're not overgeneralizing, but like with just not enough data, like we can put them here or there.

Speaker 1 15:15

And I know with all those regions, Eric, um how many there were. And Elena was describing loops, which are these structures, like literally like a loop, like think of a loop, because all the protein does is cool folding stuff. And you might imagine um if you have a change there, right? It could change how the protein moves and what it's exposed to, what it can touch.

Speaker 2 15:35

It's a barrier, something happens, and then it just has to change.

Speaker 1 15:38

Exactly. We just didn't have enough people in each individual spot to compare directly across them all. So that's why we ended up grouping those and just taking what we can do.

Speaker 2 15:49

Yeah, and generally these kids have these characteristics if they're here or if they're there. And I know um you had mentioned mutations. Um maybe I'm I can't remember, but I thought there was like there's something that might have a deletion in there too. Like it's missing something. It was mutation, deletion, and maybe there's a third one.

Speaker 1 16:09

Yes, great point. I'll comment on that too. Because Elena's lead author paper was focused on a very specific type of mutation called a missense change. And those changes are one letter change. Isn't that crazy? That one letter change in your DNA can be so different.

Speaker 2 16:25

Don't they have to be like going back to my middle school, high school science, like the the guanine and cytosine, like there's always like those two always there's always pairs, and then all of a sudden, like, what where'd this one go? Let's throw this one away. But somehow that one's in there, and like you're not supposed to be in there.

Speaker 1 16:42

That's kind of how it exactly. And so it's that one base pair change called a missense. And um, actually, I would say 90% of known patients, at least registered with us to date, have a missense change. Um, but there are other ones, like you said, called deletions, and there's quite a few other ones that essentially do the same thing in the body as a deletion called a nonsense change or a truncation, where essentially it prematurely stops the gene from actually making the protein. So you only end up with one good copy. So half, if you can think of it as half of what you need. Um, and we just didn't have enough people enrolled with those changes to include them in this analysis set. But I think what Elena said is a good plug for Simon Searchlight because it does take a lot of time, I'm sure you know, Eric, but it's really worthwhile for us to take a look at that data and be able to extract things. And while we did find some changes, as Elena mentioned, like hypotonia did stand out as being more prevalent with the loose.

Speaker 2 17:47

There's a lot I feel like they do.

Speaker 1 17:49

Yeah.

Speaker 2 17:49

Yeah.

Speaker 1 17:50

And so there was a lot of people.

Speaker 2 17:50

Late to speak, hypotonia, like exactly like that.

Speaker 1 17:55

Um, I thought what was also cool is we found shared symptoms across all of them, regardless of where their variant was. And so we ended up calling them core symptoms. Um, so those included like speech language delay or um nonverbal speech issues. Um, sleep issues were a core finding.

Speaker 2 18:17

We never had that, but I I know multiple families were like, oh my gosh.

Speaker 1 18:21

Yes. And I think that's a great point, right? These are it's not necessarily that we want to find differences, um, but we can also focus on these core symptoms as things that might be useful down the line for clinical trials that might benefit, you know, the vast majority of people.

Speaker 2 18:37

You know, taken off of, oh, oh, maybe, maybe, maybe, and okay, you got seven maybes.

unknown 18:42

Yeah.

Speaker 2 18:42

Let's take a look, you know, whatever it might be. I think one of, yep, and obviously they overlap other things.

Speaker 18:48

I think one of the coolest moments for me during my internship experience was at the conference that you mentioned, Eric, that the foundation hosted in Denver, Colorado last summer, was when there was an opportunity for the clinicians and the scientists in the room to have an opportunity to have dialogue with the parents of these children that were registered in Simon Search Site and even new families that attended this conference. And hearing you all excited to hear that sleep was something that really pulled out as a major OCNDS symptom and kind of initiating a lot of dialogue of okay, that could be playing a role in my child's seizures because not every child was having severe seizure symptomology. And so that was kind of shocking to find that not as a core OCNDS symptom.

Speaker 2 19:33

And so But there's the correlation of like, oh, maybe those kids with elevated seizures were having bad sleep, and like, oh, body's not resting, it's going to, you know, those kind of correlations where if you're living a day-to-day, you're like, oh my god, I'm just tired, I don't really care, whatever. But someone from the outside can look and like, how's their sleep doing? Not good.

Speaker 19:54

Yeah.

unknown 19:57

Yeah. Yeah.

Speaker 19:57

And so, Gabrielle, maybe you can even speak a little bit to how those conversations that the clinicians heard, you got to facilitate a conversation of how that would guide the research the foundation would then pursue.

Speaker 1 20:10

Yeah, um, that was a really, really great brainstorming session and collaborative. It was really cool. We had a part of it where the clinicians got to ask the families questions and then we did vice versa. And so this led to us creating, you know, a temporary list of priorities, at least that will guide research over the next few years. And so the things that emerged as sort of top symptom-focused priorities are sleep, like we have been mentioning, which has led to a specific sleep-focused study in a fly model. Uh, preliminary data has already indicated that there are differences in circadian rhythm patterns depending on where their mutation is. So our hypotheses are definitely showing some differences there. Um speech and language, as I mentioned, at least in our cohort of uh 48 people with the missense changes, all of them had some sort of speech issue. And so we have initiated an amazing speech and language study with an awesome researcher from Australia, Dr. Maya St. John.

Speaker 2 21:15

Yeah, I remember from the conference. Yeah.

Speaker 1 21:17

Yeah. We are almost to our enrollment goal. So another shameless plug. We're trying to get 50 people. And she is incredible. We'll meet via Zoom at all times of the day, as you imagine the time zone in Australia.

Speaker 2 21:30

That would be awful.

Speaker 1 21:32

Um, and there are multiple languages people can participate in. And we we think this will be a huge next step to actually defining what speech and language differences are taking place in OCNDS because traditional speech therapy is not often working for the kids, and we don't want to keep repeating something over and over and you know, parents paying for it, fighting insurance if it's not working.

Speaker 2 21:54

Right? Same thing over and over again, expecting different results.

unknown 21:57

Yes.

Speaker 1 21:58

And then anxiety also. Came up as a potential driver behind some of the other problem behaviors, including like uh aggression or self-injury, you know, resistance to sleep, things like that. So we're trying to see with our existing models, which is quite difficult as you might imagine, to model things.

Speaker 2 22:18

You know, a fly does with speech.

Speaker 1 22:20

Right, exactly.

Speaker 2 22:21

Eric, exactly.

Speaker 1 22:22

Um, so there are some proxy models with our mouse that we can do. So we're exploring validating that to see if that's something we could measure. And that would be quite useful if that pans out. As you can imagine, we could do some drug testing with drugs that are already on a pharmacy shelf to see like, could it help alleviate something and do some trial and error there? So it's really those discussions really have amplified our focus points for what we want to fund. Um, and we just released a pilot grant through um University of Pennsylvania's uh Orphan Disease Center for $50,000.

Speaker 2 22:59

So the orphan disease uh just ones that people forgot about, or that works.

Speaker 1 23:06

Yeah, right. Yeah.

Speaker 2 23:07

It's uh I remember hearing of them before, but I can't remember.

Speaker 1 23:10

Yeah, I I've always viewed it as like a fancier term for rare, but um I might be wrong on that. But they um help us for free to facilitate a grant program, which is really nice because it takes a lot of work to Oh, I know where I heard it from.

Speaker 2 23:27

Um when I went to DC, uh our congressman. I always forget because we only have three total people that are there. Um uh John Barrasso is the head of the rare disease caucus in DC. And he was talking about how they have like an or I think it was called like an orphan medication or orphan medicine program. So basically those the it maybe it was made for seizures or um you know restless legs syndrome, but yeah through repurposing of those drugs for other things. If one foundation or one something says, hey, we we're reusing this, they automatically put the tag on it and it never goes away. So they don't have to like redo it, even though like Pfizer, I don't know, whoever, you know, like the big company is like it's not making us any money, like, yeah, but you can't stop using it from um making it because these guys are using it or that. So I thought that was kind of a neat, like, oh, I never thought about it that way.

Speaker 1 24:26

There's a lot on that policy and that kind of ties into the science, and you said drug repurposing, so it's another ongoing project we have. And and so we've taken these priorities and we put we put them out there for this pilot grant. Um, and $50,000, right? That's a lot of money just thinking about it. When you think about research, it's actually quite a small grant. Um we think about the labor, the people, the students, reagents, etc. And so um, I was very shocked and just super enthused that we had 27 letters of intent for this grant to come through. 27 different people that are applying. Um so we're going through those now. We've invited a subset to submit a full application, and um, hopefully some of these priorities will get uh some more attention moving forward. It stood out to me from parents. Um, one of the clinicians, or actually I think it was a basic science researcher, asked families what their child's special skill was. And I thought that was just a unique framework to bring some positivity, and the memory came up. People were saying my kid has the most insane memory of like routes to school, they'll get mad at me if I take a different way.

Speaker 2 25:40

They know almost immediately, like, no, no, nannapapa. But we're just we're on a different road.

Speaker 1 25:45

Yes. Yeah, and they think that might also contribute to anxiety if you can think about maybe a bad blood draw from three years ago. You might have forgotten about it and gotten over it. But if your child has like this crazy good memory, it probably sticks with them and and probably contributes to that anxiety. So that was something novel that came through that I don't think would have come out naturally if not.

Speaker 2 26:05

No, and I like like you said, that's a really great way of kind of putting it because we always hear like, oh, we can't do this, they can't do that, they can't do that, but like they can do some really cool stuff. Yeah. I'm like, oh. Uh so Dr. Rushing, I know uh my wife and I went through the genetic testing with Ronan when we had that mom gut feeling that was like just not progressing where we wanted it to, something else, maybe. We did the genetic testing and got the report. We're like, oh, there's a lot of words we don't understand, or this or that. And I think I kind of understand what's in here. And we went back to even the genetic counselor in billings, and the lady was like, Here's some pamphlets and research papers that we found. And Miranda's like, Yeah, I have all of these highlighted. So anything new. Um, but you know, uh in the parents' mind, like, oh my gosh, he has uh an ultra-rare disease. None of us had it, I don't think, right? We're kind of going through our head, like, I don't have any of the symptoms, Miranda doesn't have any symptoms. Like, um, would you mind taking me taking us through kind of okay, we've got the report, everything, and then how how uh OCNDS or through the CSNK 2A1 specifically, all that happens and goes through a human.

Speaker 1 27:20

Sure. And yeah, I just want to validate your story is very very similar to many people in our community where they're you know something's gut feeling off, or there's like a delayed milestone by a bit too long, and so genetic testing comes into play. And so most people are diagnosed through types of genetic testing called whole exome or whole genome sequencing. And I know we're gonna have a genetic counselor on here for a future guest, so I'll save the details on that for that episode. But in short, most people with OCNDS have what are called de novo or new mutations, meaning it's new in that child and it's not present in either parent. And the way this happens is uh spontaneous or random, and it's just simply a change happens during development, during the DNA repair process, and it doesn't get caught and fixed.

Speaker 2 28:08

So it's just uh like something that people like, I know it's always one of those things that you hear from parents, like, oh my gosh, if Daddy eat that fish, did the fish do that? You know, like, oh my gosh, you know, they they kind of everybody runs to it runs to their head of like, what did I do wrong? It's always a lot of people.

Speaker 1 28:24

Yeah, it's it is not anything that anyone did. Um, it just happened randomly and didn't get caught. And the the numbers we have today, at least estimates, and again, we're we're limited by who we've found so far. The estimated um numbers are one in every 100,000 births would have someone with OCNDS. Now, if you think about that number, that's a lot still, even though we're rare, that's a lot. And so we're still facing this challenge of finding our people. So because it was just discovered in 2016, you can imagine there are probably many people who underwent genetic testing prior to that with negative results that don't know that they might have OC and DS or maybe something else, right? And so we've been big advocates for making sure the CSNK2A1 gene gets onto panels that people use for genetic testing for things like autism, epilepsy, other related uh Down syndrome, all the stuff that's yeah, that you would be tested for. And um so yeah, it's it's nothing apparent dead, it's just random, and and that's why we exist, right? We want to make sure that once a family has this diagnosis, they have somewhere to go and are not just handed one paper and saying good luck.

Speaker 2 29:42

Oh you can read it. Thanks. Okay.

Speaker 1 29:56

Um, down into a lay language that you can understand. Um and it's been quite a challenging but awesome journey to do that as well.

Speaker 2 30:06

And I feel like our our community, at least with OCNDS and the foundations, that I feel like there's a lot of people that will ask questions and like, oh, how how? And then a lot of people like, oh, okay, I understand that. Maybe it's like this and be able to work those parallels. Just mine works differently for everybody.

Speaker 1 30:23

Yeah. And there there are a handful of cases of um where someone, an adult, did have OCNDS, maybe a milder form, or it just wasn't caught, and they did have a child and did pass it along. They are very few. Um, but I will also save that for the genetic counselor um podcast because I think that would be a really great discussion for you guys to have more detail on.

Speaker 2 30:45

Absolutely. And I know um we went through two rounds of genetic testing. Um I I don't uh I don't know if we have a quick time to kind of speak to if parents are they think, or maybe they know somebody that maybe ah they're on the fence. What would be like the best so they could just do like one? And a lot of the times cost is there. Oh, and I totally forgot to bring this up. I'm gonna do it now. Um when Ronan is going through speech therapy through our hospital, um, he has private um hospital has some, the school he goes to has uh speech, but the hospital depending oh and uh I had insurance through uh company A. My wife had insurance through company B. And company B would pay for X amount of visits to a specialist um because they have a medical need for it. My wife's company B would do that. My insurance company A would not because it is not rehabilitative if he's never had the ability to speak.

Speaker 1 31:56

Fascinating. Yeah.

Speaker 2 31:59

So if he had spoken, lost the ability, and we were trying to get it back, they would cover it. But because he's never had the ability, that's habilitative, and we don't cover that. That's hard.

Speaker 1 32:09

There's similar, um, yeah, there's similar barriers to the genetic testing as well. So, in my opinion, the best route would just have everyone be whole genome sequenced, which means your entire genome is sequenced, you can go look through the whole thing. But clinicians are often limited by what they know about your child and then your insurance or your ability to pay out of pocket. So whole genome sequencing ends up being on the more expensive range. Um, so what they'll do is start with maybe what the most obvious might be. So it might be a panel of really more, or should I say, less rare conditions that more likely. Because a lot of neurodevelopmental disorders do share a lot of similar phenotypes. And then when that becomes negative, then your insurance will approve round two, which might be a more targeted panel, depending on what feature you're most concerned about or the clinician's most concerned about. There are more targeted like seizure panels or more like behavioral autism panels. And if that doesn't pan out, then they'll move forward to some of these more comprehensive ones. And that's mostly when people end up finding something in the panel. But it is, yeah, I empathize it's quite frustrating because if you just go to the end, maybe you can have the answer sooner. Um but we also have some. Yes, the cost is a thing. We also do have some partners listed on our website that if people um do suspect their child has OCMDS or a similar neurodevelopmental disorder, there are a couple different initiatives going on that might be able to offer them free testing. Um, one of them is called Probably Genetic, one is called Project Find Out. They have different age ranges and requirements, but I do think that's worth um putting out there that there might be some resources for testing.

Speaker 2 33:58

Probably add them to their show notes too, for those parents who might be interested in the world. That'd be great, yes. Perfect. So, doctors, um, we just talked about going through our genetic testing and and getting that report. What's one piece of advice from the very educated side of genetic testing that you a piece of advice you would give parents that just got that report or just have been able to absorb that their child has maybe an ultra-rare or just a rare disorder?

Speaker 1 34:31

Yeah, I think my main point is you're not alone. We've really built a strong community, even outside of OCNDS, right? There's a larger rare disease community, and there are people in your corner and there are people working really hard to try and find answers. Um, but my main piece of advice is you can make a difference. Just you and your family. Every small thing you do to contribute, whether that be talk to another parent, signing up for research, that small act adds up over time and lets us find out more and be able to give that back. So don't ever underestimate your contributions.

Speaker 35:06

And Elena, do you have any? No, I love that, Gabrielle. I think mine would be that, especially coming from a basic research background more recently and really getting my footing in the rare disease community. I would say to don't to not, I'm sorry, I would say to not underestimate your barrier to entry. I think if you are interested in first pass joining through a Facebook group, the community is so much stronger and wiser because of people choosing to participate and ask questions that they might be scared to ask, which is why you, Eric, are such a wonderful host for asking questions that parents are constantly thinking about and for you to revisit all that. I think it's just a really helpful roadmap, as you say, to navigate this. So yeah.

Speaker 2 35:54

Yeah, thank you. Um it is it's you know, thinking like I'm sure people if they if they read it, it helps my wife works at a college. So the math uh uh teachers were helping, and all the other people were like, I can nerd out and see what I can look up and find. And the the research librarian was like, Oh, I got this. Started looking up stuff for her, too. I know you mentioned about Simon Search Light. That's a big one if parents feel like they have is that something that a parent can do, can reach out to Simon Search Light if they're not part of a foundation or something like that, like, hey, we have a diagnosis.

Speaker 1 36:29

Yeah, they study um many autism-related genes. CSNK2A1 is one of them. We have links on our website, and we can definitely put it in the show notes. That's that's one of our main research initiatives. We do have a handful of others. One collects medical records on your behalf called Citizen Health, which I find amazing because they collect them all for you in one spot. And then if you go see a new doctor, all you have to do is go share.

Speaker 2 36:54

Here's everything.

Speaker 1 36:56

So I know that saved people a lot of headaches and time, and we've also used it internally for research to help um simulate some medical case reports to highlight new symptoms out there. And so yeah, there's a ton of research going on. I encourage you to check the website. And if anyone does have questions, um I am available via email, just as Elena said. Feel free to reach out and I'm happy to have a conversation.

Speaker 2 37:19

Perfect. Well, thank you both for for being uh a great part of this discussion and kind of getting our the podcast off the ground and going. And uh from a parent to doctors, we appreciate what you guys are doing and the the time and the effort and everything that we never see except for that paper or the the presentation. Like it's hours and and I mean thousands of hours, I have no doubt, of looking through and making it and taking I and I love uh my wife and I are part of the parental advisory board for the foundation. So seeing some of that, like, hey, what do you guys think about this? And like hearing the like oh we put a lot like this this is really and like well, how about just like a change in the color or you know, like little things of oh, oh yeah. Yeah, and you guys take feedback and we we understand better when you guys talk through it with us too, and appreciate all the time and effort you guys put in, either intern or right.

Speaker 38:17

Aw.

Speaker 1 38:18

Thank you, Eric. This has been great. We really appreciate you diving headfirst into this series and taking the reins. Um really excited to see you grow.

Speaker 38:25

Thank you so much, Eric. This was awesome.

Speaker 2 38:27

Thank you guys again, and we'll hopefully see everybody uh on our next episode.

Speaker 38:32

Awesome. Thanks, guys.