Why join the Relutrigine study from Praxis for DEEs with motor seizures? – #S10e176
Wed July 30, 2025
Audience: Any family with a DEE who has a kid who has seizures, yes SYNGAP1 is a DEE and you are always my first audience.
See #S10e133 if you are curious about DEE vs other names. https://curesyngap1.org/podcasts/syngap10/what-is-this-syngap1-illness-disease-syndrome-ndd-dee-mrd5-nsid-actually-called-s10e133/
Action: If your kid has motor seizures, fill out the screener and join this amazing study.
Link here: https://www.resiliencestudies.com/emerald
A motor seizure is a seizure where you can see something moving – including head drops, drops, convulsive, etc. – only excluded seizures are absence, myoclonia and infantile spasms. You don’t need to figure this out, just fill in the screener, let the doctors figure it out.
Questions: Come to live webinar tomorrow, it will not be recorded, so you have to come register here!
TRIAL
Any DEE patient with 4 motor seizures a month, minimum.
Age 2-65. Adults are you listening?
24 weeks (6 months) weeks, placebo controlled but everyone will get drug at some point in the trial.
28 weeks (7 months) week OLE, with a chance for expanded access, so if it works, you can stay on.
Fully decentralized, you don’t have to go to a site if you don’t want to.
One US site open so far in Bethesda, there will be others. Int’l sites in 2026. US ENROLLING NOW.
DRUG
Lots of science and big words in the links below, but here is what you need to know as a parent.
1. It’s a liquid, can go oral or in a g-tube.
2. There is no ramp up, you put it in and it works. In terms of speed, think Lorazepam not Lamotrigine.
3. It’s potent and specific, which means small volume. Roughly 1ml for 10 kg. This will be a rounding error in the face of a normal Syngapian med regime.
4. Even though this is a sodium channel drug, it should benefit all DEEs b/c, good to clarify tomorrow, all seizures end with a hyperactive sodium channel firing and that is what Relutrigine focuses on.
PRAXIS
Serious people, lots of work on Epilepsy. Connected to SYNGAP1 and DEEs, just need to move faster on SYNGAP1 ASO!
1. CSO is Steve Petrou, works with SRF AUS and knows they are waiting.
2. KD and AN started a company for SCN2A and it was absorbed by Praxis, they are still there and are relentless.
3. Work on both small molecules and ASO, this is a way for them to see our team in action.
Cool links:
AES 2024 Story
Embold read out
FDA Breakthrough
More links
Why am I doing this?
1. We need better meds and the way to meds is through trials.
2. We need to jump at every trial, every time.
3. This one is decentralized, so minimum burden.
4. If you get in now, this will be over before it’s ASO trial time, so you could do both.
5. Our Syngapians with motor seizures tend to be our most severe, we have to make sure we find out if this drug can help. All our kids may progress to this point.
See you at the webinar, fill out the screener now
Below is a transcript from the video:
Mike Graglia
[00:00:00] Hello, Syngap land. My name is Mike Graglia, and this is episode 176 of the Cure Syngap1 podcast. Today I’m going to talk about one thing and one thing only. Why you should consider the Relutrigine study from Praxis for DEEs with motor seizures. I want to be clear at the top, my audience here is always first Syngap families, but anyone who has a child with seizures, motor seizures, from a developmental and epileptic encephalopathy, or DEE. And that just means a genetic disease that causes seizures, by the way. This applies to you. This is worth listening to because all I’m going to talk about is this drug and this study. And guess what? If you have a DEE with motor seizures, like SYNGAP1, you could take part. Now, if you’re like, what is a DEE? I don’t understand. I talked about this in episode 133. Go listen to that for your edification. I’m not going to talk about it now. The punchline from today is if your child has four countable motor seizures a month. If you can see them moving their body, head drops, convulsions, status, whatever, four times a month. You qualify for this seizure. And you should go right now to resilientstudies.com/emerald. Link is in the show notes. And click, see if I qualify. Fell out the screen or they forward it to a doctor. Doctor calls you. Let the doctor figure it out. Don’t spend time thinking about, wait, am I, should I? I don’t know. Just click the link, fill out your information. They’ll get you on the phone with a doctor. Doctor will help you figure it out. But I really think if you have a DEE patient with four or more motor seizures a month, you should check this out. What if you have questions? What about this? What about this? What about this? There’s a webinar tomorrow. SRF is hosting it with the team from the company who’s doing this. And it’s at 1 Pacific, 4 Eastern. So if you’re in the U.S. And you can make it at 1 Pacific, 4 Eastern. Make it to that call tomorrow. They will present all their stuff. They’re going to be a lot more interesting than me. And they’re going to be able to answer your questions live. Because it’s recruiting for a study, they don’t want it recorded. There’s so many rules around these studies. It’s bonkers. So it is a live study. And one of the reasons I’m pushing this podcast out today is to urge you to come to that webinar live because it will not be recorded. Let me just throw out some fun facts. I want to make sure you hear this from me, and then you can hear it again from them and check my facts. This is for any DEE patient with four motor seizures a month, at least. I already said that. The age range is from two. None of our kids start seizing before two, so that’s great, to 65. Freaking amazing, right? So all the adult patients out there, the 20s, the 30s, the 40s, the 60s. Well, I’m afraid Karen’s too old for this one. qualify for this if they are still struggling with motor seizures. I’ve talked to at least one mom who’s definitely got an adult with a lot of motor seizures. I think he’d be a great candidate. The study is 24 weeks long. That is six months. It is placebo controlled, but everyone in the trial will get drug at some point. What that means probably is that half will start on placebo, half will start on drug, and then the placebos will get drugged. I don’t know. Ask them. That’s just my guess. But it states on their website. that it’s 24 weeks long. and everyone gets drugged at some point in the trial. Better news. Once the trial is done, if you want, there is an open label extension for another seven months. So if the drug works while they’re dealing with regulatory approvals and all that madness, you can stay on drug for an additional seven months. And if you’re seeing incredible benefit. They say that there’s a chance for expanded access. And what that means is basically getting access to the drug. It doesn’t matter. The point is, if you get on this trial and the drug helps your kid, you can stay on the drug for the foreseeable future, which is pretty exciting. Here’s the thing I’m most excited about with this trial, aside from the adult thing. The adult thing is super cool. and the open to all DEEs, right? SLC6A1, Syngap1, SCXBP1, all the SCM whatever’s, all these CTN and B1. USP 7. Now I’m just thinking of my friends. KCNT1. Everybody who’s got seizures can do this. Pretty exciting. KCCNQ2. This study is fully decentralized. This study is fully decentralized. What does that mean? You don’t have to set foot in a clinic. They will come to your house. They will come to your house. The way it works is the PI, the principal investigator, will be telehealth and they’ll be talking to you. They’ve got the big picture, but they will pay for a doctor and a nurse to come to your house. The doctor will do doctor stuff and do assessments and the nurse will draw the blood and help, right? And then they will come to your house every, I don’t know, month or so. I’m making this up. And you never have to go anywhere. And this I think this betrays lessons learned by this company around how hard it is to deal with our kids sometimes. And somebody just said, well, why, why are we making them come to a clinic in the first place. And that has really earned my respect. And I want to see this trial succeed because I think this model should be the rule, not the exception, right? So far there is one site open in Bethesda these opening sites i’m learning takes forever and and so there’ll be other sites but with this decentralized business it don’t matter They can telehealth you from Bethesda. And they can get a doctor or nurse to come and see you live. Apparently, there are international sites planned for the future, for 2026. But the U.S. is enrolling now, people. So if you’re stateside, you could enroll in this. And I think it’s pretty exciting. Why do I think it’s exciting? Okay, there’s lots of links at the bottom of the show notes. There’s a link to more links. Lots of science, big words, really exciting. I’m not going to regurgitate words I barely understand. I’m just going to tell you some cold hard facts that I heard from the company. First of all, this is a liquid. No more tablets to swallow. This can go in the mouth. This can go in the G-tube. Pretty cool. I’m talking about the drug. Number two, there’s no ramp up. You put this drug in, it works. Take the drug out, it stops working. Right? Small molecule. We’re not talking about ASOs. Think, I mean, many of us have been on Lamotrigine. Lamotrigine is one of these drugs with really slow wrap up and you start giving it in like June and you figure out if it’s working by the end of July. I don’t like that. But this drug, you give it on Monday and you know if it hit on Tuesday, right? So I like that. There’s no ramp up. It’s much more, it’s not really as fast as Lorazepam, but like on the spectrum of Lorazepam to Lamotrigine, it’s like right here. So I like that a lot. It is potent and specific. Now I’m getting into technical terms, but potent we all understand. Specific means it goes right to what it needs to go to. The real life implication of potent and specific is that you don’t need to drink a jug of this stuff. There are certain drugs that will remain nameless. Some of our patients are on and they’re like. Parents are bringing it home in suitcases. Suitcases! I’m not making this up! Well, Lutrogene, you’re talking about, and check my math on this tomorrow. From what I understood, it’s like a milligram, milliliter. tiny, per 10 kgs. Right? 10 kgs is 22 pounds. Your kid weighs 100 pounds. That’s five milliliters. I mean, if you looked at what you give your Syngapian in a day, and I’ve seen a lot of pictures of a lot of counters full of drugs and syringes. ML per 10 kg is Nothing. nothing for a rare disease parent. So I think that’s a pretty exciting feature of this drug. And then this question will come up as you start looking at it. This is selective for a hyperactive sodium channel. And what everyone’s going to say is, oh wait, sodium channel, that means SCM1A, SCM2A, SCM8A. You always wonder what happened to 3, 4, 5, 6, and 7, but whatever. Those are the big three SCNs, one, two, and eight. The point here is, people hear that and they’re like, oh, it’s just for those. But that’s not true. The truth is when the brain seizes, apparently, now I’m just parroting stuff I’ve been told. I don’t know if this is really true. I don’t know. It’s not like I studied this. When there’s activity that leads to a seizure, one of the last steps in that chain is a hyperactive sodium channel, regardless of if you’re whatever gene you are, right? And it’s that hyperactive sodium channel that gets hyperactive right before we seize. So this drug selectively, meaning only, goes after those hyperactive sodium channels that are about to allow a seizure to happen and says, uh-uh, stop that, sit down. And can you tell I’ve been hanging out with my seven-year-old? and And so this drug, even though it acts on hyperactive sodium channels, should benefit everybody with a seizing brain or a DEE. So that’s pretty exciting. So that’s mechanism of action. I didn’t share that with you. Because I want you to think about it. I shared that with you because some people get derailed when they see Sodium Channel. Don’t let that happen to you. I want to talk briefly about Praxis. Because everyone’s like, who is this study? Who’s behind this? Praxis is a company SRF knows pretty darn well. I’m going to say nice things about them right now. They’re serious people. They work hard on epilepsy. They like to say they’ve got the biggest epilepsy pipeline. I’m sure it’s true if they just keep saying it. They are very connected to Syngap1 and DEEs. My only polite, respectful criticism for them is, guys, please hurry up and get your ASO out the door. I know they’re working on a Syngap1 ASO, and I’ve been asking them to just bring it to the market soon. But that’s the only thing I’m going to say that’s not positive. Their CSO is Steve Petru. He knows what Syngap is. The Australian Syngap community is all over Steve. He knows that they know where he lives and he knows that we are waiting. So Steve’s a great guy, and he’s a serious scientist, and so he knows how to spell Syngap1. Praxis is led by a very serious and fast-moving individual named Marcio Souza, Brazilian, great guy. And at some point, Praxis merged with, absorbed, whatever, a company called Rajcon, which was founded by if I’ve got this right, Alex Nemirov and Kelly Dalby. Alex and Kelly are people I’ve met, people I met very early on. And they, to their credit, decided to start a company, not a foundation. And they started work on SCN2. They actually contracted work from Steve. And then Praxis got involved with Steve and just absorbed the whole thing. Kelly and Alex, who were parents just like us are still at Praxis in leadership positions. So this isn’t some like nameless, faceless drug company far away that’s working on us because we scored well on a whiteboard, right? This is Marzio, Steve, Kelly, and Alex who get it, who know what Syngapians look like, who understand what DEEs are, and are working like hell to make better medicines. And I really appreciate that about them. I think they’re cool people. Like I said, the only thing I wish they would do differently is hurry up and get that damn Syngap ASO out the door. But! They are working, I should point out, or as should be obvious from this talk, on both small molecules, which Relutrigine is, and ASOs. I won’t tell you about all the ASO work they’ve done, but Syngap is definitely on their pipeline on their website. And so one of the reasons I want Syngapians to do this trial is I want us to benefit from this drug because it looks like a promising drug. And we want to know if it works on Syngapians. And I want Praxis to see how Syngap families show up and jump into trials. So that’s my brief pitch on the trial, on the drug, and on Praxis. There’s some links in here. They just got breakthrough designation for 2A and 8A. from the FDA like two weeks ago. There’s an article about the Embold study. Embold came before this study. It’s just a lot of exciting data. There’s a cool link about a poster that came out at AES. And this was a kid. I think they had one of the A’s. And they were seizing like crazy, baby seizing like crazy they got this drug back in 2024 and seizures and status epilepticus went down radically. It was pretty exciting. It was pretty exciting. So that links in the show notes. That’s the first time I heard about Relutrigine. I’ve been following Relutrigine ever since. It’s over almost two years now. And finally through this Emerald study, which is visionary on, I think, visionary might be a little strong. Cutting edge is not, though. This study is cutting edge in that it is fully decentralized and it is open to all DEEs. In the old days, it wasn’t decentralized. You had to schlep into a lab, and it was for Dravet. And good luck if you don’t have Dravet. We’ll get to you later. So I think the fact that they’re opening this up to all DEEs and they’re doing it fully decentralized is just really exciting. And someone’s going to ask me, Mike, you were really positive on this. Why’d you do this? Are you getting paid for this? I’m not getting paid for this, right? As you know from watching the previous 175 episodes of this podcast I am neck deep in this space. And when I see something I get excited about, I’m not afraid to say so. But let me answer the question, why am I doing this? One, we need better meds, and the way to get better meds is to go through trials. We have to start getting used to jumping into trials, checking stuff out. So we have to jump at every trial, every time. That’s point number two. Mike, hey, Mike, look at this trial. Should I do it? My default answer is yes. We should look. We should go through the screener. We should talk to the doctors. We should talk to our doctors, all the things. But yes, if there’s a trial, if people have spent the millions of dollars it takes to get this far, that’s probably a drug that we should be looking at. This one is decentralized. I already told you how exciting that is. I want to go back to the timing point because this is super interesting. We’re in July. If you screened tomorrow and got enrolled and started dosing in august. August, September, October, November, December, January. You’d be done with the six months. By January, I am hopeful that early or mid-next year, as I’ve said before. CAMP4 might start recruiting for their ASO truck. So if you’re thinking, wow, my kid has a lot of motor seizures, but I don’t want to get excluded from the ASO trial, so I’m not going to do this trial. Check your date math because there’s time. There’s time to do this one now. Get through the six months. And then hopefully you’re benefiting from the drug. You stay on the OLE. When the ASO trial rolls out, you just wash out of this drug. You just stop taking it, wash out. Your seizure is going to come back, but then you can do the ASO trial. Conceptually, right? It’s really, the timing is good for us, guys. So if your child is seizing four or more motor seizures a month, Get on it. And then the other point I’m just going to make is. Our Syngapians with motor seizures are not the majority of our community. But they are some of our most severe cases. And I want to make sure that everybody hears about this trial and that they consider it. So if you know another Syngap parent whose kid’s having motor seizures, please encourage them to consider this. And I want to say a second thing there. Unfortunately, what we see is that as our patients age, seizure frequency, severity and variety, meaning the different kinds of seizures, increase, right? And we’re funding work with Dr. Juliet Knowles, who’s just exceptional, is part of the Stanford team, looking at why it is that Syngapian seizures progress. And I’m not going to hit you with that right now, but it’s a thing. Right. Just because a Syngapian has mild seizures at five does not guarantee they’re not gonna be dropping like crazy at 20. So, all of us have an interest in understanding if Relutrigine effectively addresses Syngap1 seizures, all of us. And so please share this video with other Syngap families, encourage them to come to the webinar tomorrow. If they missed the webinar, just go and screen and check out this trial. If you have questions, of course, call info@curesyngap1.org. We will answer your questions, but it’s better to ask the company. And it’s better to see if this drug could help your loved one. The link for the trial is the last link in the show notes, resilientstudies.com/emerald. Please check it out. Thanks for listening.