Transcription:
Genetic Epilepsy: Finding a Cure

Bill Klaproth: Host: So why is it important to identify genetic epilepsies and other epilepsies that children have? How are genetic epilepsies currently treated and what are the new cures on the way? Well, let's find out with Dr. James Wheless, Director of the Comprehensive Epilepsy Program and Neuroscience Institute at Le Bonheur Children's Hospital.

This is The Peds Pod by Le Bonheur Children's Hospital. I 'm Bill Klaproth. Dr. Wheless, thank you so much for your time. It's always great to talk with you. So let's start with this. Why is it important to identify genetic epilepsies and other epilepsies that children have?  

Dr. James Wheless: Yeah. One of the things historically is we've treated all children with epilepsy, no matter what their cause was, with the same medications, the same treatments. In the modern era, what we've come to realize is that we should tailor our treatments to the cause of the child's epilepsy, when we know that and for some, that could be a real-game changer.

Host: So more of a targeted, specific way to treat it.

Dr. James Wheless: Exactly.

Host: So then how can parents find out if their child has a genetic epilepsy?

Dr. James Wheless: when we think of genetic epilepsy, maybe some people do, like who's your mother, who's your father. We're thinking of are there passed down traits that run in the family or new traits that show up in the child that are causing the epilepsy. Individually, these are rare. But there's hundreds of those now that we've discovered. So collectively, they make up a good chunk of the children we see, especially preschool age. Most of these are diagnosed based on a simple blood test and some even now done off a saliva or spit test.

Host: So then when it comes to treatment, Dr. Wheless, how are genetic epilepsies currently treated?

Dr. James Wheless: When we treat epilepsies that have a genetic basis, historically we've kind of borrowed, if you will, or used medicines that have been approved for the same seizure type in folks with other causes of their epilepsy. So we kind of said, "Gosh, it works for this seizure type. Even though you have a different cause, we'll just use it over here for your child." In the modern era, what we started to do is do treatment trials that only include children with certain types of genetic epilepsy. So we've been able to start to look at very specific drugs that work for them. Now, some of those may also work for other causes. We've actually had their first trials ever in the last few years where we've just looked at only certain genetic causes and said, "We're just going to see how well this drug works for your child."

Host: So prior to this research work and drug trials, how were epilepsy is treated.  

Dr. James Wheless: prior to that, we were using the same medicines we'd use for everybody else. We just were thinking, "Gosh, if they work if he had head trauma as your cause of your seizures, maybe they'll work if you'd have a genetic cause if you have the same seizure type. So we're kind of borrowing medicines that we already, used to treat seizures. But we weren't really saying, "Do they work better or are there better ones to use if you have a genetic cause of your epilepsy?"

Host: Right. So are there new cures coming down the pipe for epilepsies?

Dr. James Wheless: Yeah. So for our genetic epilepsies, I mean, one, it was a huge shift just to say we should look at medicines to see if there are certain ones that worked better for them to treat their seizures. But then a real change in our thinking as physicians came out, we said, "Well, wait a minute. They have an underlying genetic cause that's affecting kind of chemistry in the brain that causes the seizures and we're just looking at a treatment for the seizures, so we're kind of putting a band aid on it, if you will. Why don't we maybe back up and say, 'Can we fix the underlying genetic neurochemical changes in the brain? Because if we fixed that, then we don't have to worry about the downstream seizures. They won't be there. '"

So for the first time ever. this is a really big paradigm shift, we're saying, " Let's treat the underlying genetic cause and not just a symptom, the seizure."

Host: Right. So kind of attacking the root cause of it. So then how is Le Bonheur involved in protocols for these new drugs?

Dr. James Wheless: So Le Bonheur has been at the forefront, if you will, of looking at new drugs for decades now in children with epilepsy. And as these genetic trials began, looking at actually using different kinds of treatments to modify kind of the genetic code of that child to normalize it if you want to think that way to where they won't have the seizures. we're actually one of the, handful of sites in the country that is involved at the very front end that we'll be looking at these new treatments. They're not traditional antiseizure medications. These are very different. They're meant to correct the genetic change that that child has and restore normal neurochemical function in the brain. if we do that, then the seizures should go away.

Host: Wow, this is fascinating. So can you give us a real-life example of a common genetic epilepsy and how we treat this now and then how this may change when we're able to treat the genetic cause or the root is, you're calling it?

Dr. James Wheless: Yeah. So one of the ones that we see, and these are all rare, one called Dravet syndrome. it's a horrible problem for the families and for these children.   Their development's on track. They then develop seizures provoked by fever that are convulsive, then other convulsive seizures just start happening on their own without fever. And then kind of add insult to injury, their development starts to tank and they actually start to lose milestones.

Historically, we've just had to treat their convulsive seizures as best we could with medicines. So we're actually, hopefully starting this fall, this winter with genetically based therapies to kind of say, "We want to try and fix the underlying genetic cause of these seizures in these children." But if we fix that, hopefully we'll also rescue the developmental changes they've had too and keep those from spiraling downhill in a negative way as well.

Host: Right. And on top of that, Le Bonheur is forming a neuroscience research consortium with St. Jude's Children's Research Hospital. So what are the goals of this new consortium? And can you tell us why it was formed?

Dr. James Wheless: thinking was that in this consortium in kind of setting it up is to use the model that we've had with treating, tumors in children that St. Jude really launched, back in the 1960s, the idea that we would start with best therapy, see how children did, and then we'd keep modifying that, keep improving it at every step.

now we're using it in epilepsy. So we know these are rare epilepsies about combining St. Jude's background what they bring to the table with their resources, their faculty, their innovations in science, with our clinical team that has been doing research and treatment of these epilepsies for decades and saying, "We want to do the same thing. We want to be the site that's the first in the country, that's able to offer children some of these unique therapies because of our combined resources."

And then once we get them doing better, we'll say, "Okay, what's the next thing to add to that? Where's the next step?" We want to keep ratcheting it up and quicker, if you will, to where we're at answering these questions and getting these children doing better quicker, much like they did the treatment of, tumors.

Host: Yeah. This is very encouraging news, not only for children with epilepsy, but for parents as well. I know this is comforting information, Dr. Wheless. This has really been informative. Thank you so much for your time. We really appreciate it.

Dr. James Wheless: Thanks for having me bill.

Host: That's Dr. James Wheless and learn more about Le Bonheur's Neuroscience Institute at LeBonheur.org/neuroscience. And be sure to subscribe to The Peds Pod on Apple Podcasts, Google Play, or wherever you listen to your podcasts. You can also check out lebonheur.org/podcast to view our full podcast library.

And if you found this podcast helpful, please share it on your social channels. This is The Peds Pod by Le Bonheur Children's Hospital. Thanks for listening.