Jason Hauptman, MD, PhD, Pediatric Neurosurgeon at Seattle Children’s Hospital talks about a trial for a medication that may help children with epilepsy.
Interview conducted by Ivanhoe Broadcast News in March 2019.
Let’s talk a little bit about the trial. After talking with Doctor Saneto it sounds like it’s super needed because there’s nothing like it out there. What led to the trial and where are we with it?
HAUPTMAN: Great question. One of the greatest challenges we have in the treatment of children with really, really devastating, tough epilepsies – seizures that are no longer responding to medication – is that, once they try surgery, which can work in anywhere from 50 to 60 percent of children, it’s the end of the line as far as the treatment options that we have. There’s still approximately 40 to 50 percent of children who, despite multiple medications and even brain surgery, continue to have seizures. There’s this incredibly unmet need in these children who are finding alternative therapies when they’ve maximized everything that we have to offer.
Where does the trial come in?
HAUPTMAN: Right now, the trial is aimed for children who have tried everything, including multiple medications and brain surgery to cure them of their seizures. If these are not working, the next step is to try this new medication, a medication that’s been used in other ways for other diseases in the past but never really for this application in this population’s children. Right now with a study, we’re looking at both safety – making sure that children are safe when taking the medication and not having a significant side effects – and we’re also looking for early signs of what we call efficacy, which is how well a medication works, to see if we can benefit these children and reduce their number of seizures.
What’s the mechanism of how the new drug works?
HAUPTMAN: For a long time, many people in the epilepsy community have thought about a particular enzyme, which is a protein when we talk about things at the cellular or molecular level, called MTOR – spelled M, T, O, R. We’ve known for years that this particular enzyme now functions in a genetic disease called tuberous neurosis of which epilepsy is a primary characteristic of that disease. However we’ve learned over the last decade that MTOR not only is dysfunctional in tuberous sclerosis, but also has a role in a variety of other types of epilepsy. This drug works on that particular enzyme or protein. And our thought is that by changing the way this protein acts in these children with epilepsy, we can, in turn, change their epilepsy.
Ultimate goal to use it to completely stop seizures?
HAUPTMAN: If I could have my way, this would be the drug that would end seizures for all children that have intractable epilepsy that doesn’t respond to medication. We’re going for improvement and even that would be a win in my book for these children. And we’re hoping for a cure.
The trial started in August?
HAUPTMAN: Yes.
How many kids are in it?
HAUPTMAN: So far, we’ve completed our first cohort, which was three children at a low dose. And we’re now about to complete our second cohort, which is another three children at a somewhat higher but not significantly higher dose.
And then will there be a third cohort as well?
HAUPTMAN: There will. So once this cohort is closed, we’re going to open one additional cohort at a slightly even higher dose. And that one’s probably going to be at least three – if not – six or more children. And that’s going to end the first phase of this trial.
Are you recruiting?
HAUPTMAN: We are actively recruiting children who have not only epilepsy that’s no longer responding to medication, but epilepsy that has also not been cured by a surgery with the intent to cure.
Any kind of timeframe as to getting to a Phase 2, and if this works, to the public?
HAUPTMAN: Great question. We are very enthusiastic about our early results. It seems like so far this medication has not really had any significant side effects. And there’s also some early clues that this could be helpful in this population of children. We’re already thinking about strongly writing the second phase and hopefully giving something online within the next year or two.
Tell us a little bit about what you’ve seen as far as results in controlling the seizures with kids so far.
HAUPTMAN: Granted, this is a small number of children. But everything we’ve seen has been promising. The parents have noticed very positive changes in their children in terms of not only seizure frequency, some behavioral issues as well and even sleep at night may be positively impacted by this. We really look forward to seeing larger numbers of children and seeing how much of this pans out over a larger population that’s being treated. But early results are pretty exciting.
That is exciting. What kind of age variable are these kids? Are they all teenagers?
HAUPTMAN: We’re recruiting right now children over the age of 3 and under the age of 26. A lot of that has to do with what our constraints are here at Seattle Children’s with children that we can’t see in the research setting. In the second phase perhaps that could be expanded. And of course we’re going to work with the FDA to see what guidance they give us as to what age ranges they want us to look at.
Because you’re using an existing drug that already has some testing on side effects and things like that, that should speed things up a little bit.
HAUPTMAN: We’re really hopeful. The FDA felt like this was a new population of children that had not been exposed to this medication in a controlled way like a scientific experiment or a clinical trial. And therefore we are starting slowly and conservatively. But my hope is that, as we move forward, it’s going to be easier for us to progress towards treating a larger number of children for this indication.
We’re super far away from estimating how soon until someone can go into the pharmacy for this, aren’t we?
HAUPTMAN: I think we’re years away. Depending on how our results look, off-label use of this drug could be something that could be considered. But I still think it’s really early for that as well.
Even for off-label?
HAUPTMAN: I think so. I think that we should do our due diligence, make sure that we’re really being safe with these children and that there’s a positive beneficial effect.
Great. What else should I ask about the trial that you think we should include?
HAUPTMAN: This is a medication that is given once a week in an intravenous form. And it actually lasts an entire week and works in a completely different way than any anti-seizure medicine currently on the market.
What do you mean by that?
HAUPTMAN: The vast majority of anti-seizure medicines that are on the market – the way I like to think of them is like they are hitting a finishing now with a 12-pound sledgehammer. These are medicines that work on the very fundamental ways nerve cells communicate and they don’t really discriminate among nerve cells. And that’s why there is always a lot of side effects with these anti seizure medicines. Because while they’re really effective against the nerve cells that are over communicative, that are two active in the epilepsies, they’re also affecting the non-epileptic nerve cells too. In this particular trial, we’re looking at a drug that doesn’t really work on the physiology or the function of nerve cells in the traditional way, but instead, it’s working at a much more focused molecular level.
So smaller target, fewer side effects.
HAUPTMAN: That’s what we’re hoping for. Certainly not some of the cognitive side effects that we see with the anti seizure medicines. And that could be a big win for these children too.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Lindsay Kurs
206-987-5752
lindsay.Kurs@seattlechildrens.org
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
