Maggie McKay (Host): Whenever your child has a disease, you want to know as much as possible. Today, Dr. David Toupin, Assistant Professor of Neurology, will discuss advancements in Child Neurology at UK HealthCare, focusing on work at Kentucky Neuroscience Institute to address spinal muscular atrophy and Duchenne muscular dystrophy.

Welcome to UK HealthCast, a podcast presented by UK HealthCare. I'm your host, Maggie McKay. Welcome, Dr. Toupin. Thank you so much for making the time to be here today.

Dr. David Toupin: It's a pleasure to be here.

Host: Let's start off talking about spinal muscular atrophy. What is this condition and how common is it?

Dr. David Toupin: Sure. So, spinal muscular atrophy, which we call SMA, it's a genetic disorder. It causes progressive weakness. And so, typically, SMA will start having symptoms in early childhood and, in the most common and severe form, often presents in early infancy. In the past, this condition often resulted in progressive weakness of the limb muscles, the trunk, and eventually affecting swallowing and breathing. And unfortunately, most children would pass away by two years of age. However, now that treatments are available, which I'll talk about later, that's definitely different. Kids are doing much, much better. It's a rare condition, typically thought to have an incidence of around 1 in 10,000 live births, which in the state of Kentucky turns out to be about five patients per year.

Host: Wow. That's five too many though. How is it diagnosed?

Dr. David Toupin: So, typically, SMA any more is diagnosed by the newborn state screen. So, in 2019, Kentucky was actually one of the first states to start using a newborn state screen to diagnose SMA. So, this means that when kids are born, they get the typical heel stick and that heel stick is sent off. And then, by four or five days of life, you know whether or not the child is affected. Before that, it often was a long drawn out journey for families to get a diagnosis with a lot of doctors visits and tests before the diagnosis was suspected and ultimately diagnosed. Any more though with the newborn screening, children are identified rapidly. They come into the treatment center, and we will do additional genetic testing to confirm the diagnosis. And then, we will move forward potentially with life-saving treatments.

Host: And you mentioned treatments. What is available?

Dr. David Toupin: So, there are three medications currently available to treat SMA. The first treatment called nusinersen came out in 2016. This was a game-changer as far as children would do with SMA. And really, what we found is they would halt the progression of disease in many children. Unfortunately, in 2016, most children were still very symptomatic. They had a lot of weakness by the time they were diagnosed. And so, a lot of those children continued to have that degree of weakness. And then really, in 2019, when gene therapy, which is called Zolgensma, the technical name is onasemnogene abeparvovec, which is a bit of a mouthful. But when that treatment became available, plus the newborn screen, it just radically changed the landscape. And then, we found that children were not only living, not only meeting milestones, but many children having very few signs of weakness at all as they would get older. So, it was a really tremendous breakthrough.

So in 2021, risdiplam came out. This is an oral drug, and so this is a once-a-day medication that also will halt the progression of disease. And so now, we really have three great options for treating SMA, and they each have their risks and benefits. But it's safe to say that SMA is no longer once the devastating disease that it was.

Host: Oh, thank goodness. Why are the treatments for this condition so novel and revolutionary?

Dr. David Toupin: They work by advanced mechanisms. So, the first drug I mentioned is something called an antisense oligonucleotide, which is a mouthful. But what it does is it acts almost on a DNA level. It works on sort of the RNA that comes from DNA and changes the way genes are expressed in the body. So, it's a complicated mechanism. And then, really, the gene therapy, which is Zolgensma, it actually adds a piece of DNA that was missing to the child before. So, in SMA, you're missing what's called SMN1, and Zolgensma actually gives your cells that gene, so that it can survive and the disease does not progress.

Host: If you think your child may have this, what are some important things to consider?

Dr. David Toupin: Fortunately, 95 plus percent of kids are now diagnosed before parents even know they have symptoms due to the newborn screen. So, for young children, for babies, the vast majority are going to be diagnosed that way. For older children who perhaps have a milder form of SMA, maybe not the most severe form that was fatal at a very young age, they could still potentially present, if they were born before 2019, with subtle signs of weakness that just seem to get worse as the child gets older. So, decreased endurance, muscle pain, having trouble going upstairs, just not keeping up with their peers, could be some of the early signs and symptoms of SMA.

Host: And what are some of the ongoing challenges in SMA diagnosis and treatment?

Dr. David Toupin: So, a lot of the challenges are now gone thanks to gene therapy and newborn screening. This disease is just a completely different disease than it was before. What we're presented with now though are very different questions. There are patients, like I mentioned, who may miss the newborn screen or have a mild type and may come in later. So, those patients may still have issues. There's also the patients who were unfortunately born before these treatments were available. They often are still quite weak, and we have not found a way to turn back the clock and give them strength that they have lost, which I think is desperately needed.

And then, I guess the other thing we have to watch for is as these treatments are new and we don't fully understand the long-term effects of these drugs, we need to monitor these children over time to, number one, make sure that they stay strong. But then, number two, to make sure that there are no long-term side effects of these medications that we just don't know about yet.

Host: So now, let's talk about Duchenne muscular dystrophy. What is that condition and how common is that?

Dr. David Toupin: Duchenne muscular dystrophy, it's a condition that primarily affects boys. It's again, a genetic condition like SMA. And unlike SMA, which typically presents in early infancy, Duchenne muscular dystrophy takes longer for people to notice signs and symptoms. So, it's often not until age three, four or five that parents will really pick up that their kid is weaker than other children and may be getting worse. Also, children tend to live longer with Duchenne than they did with classic form of SMA, so kids with Duchenne eventually will lose strength in other muscles too, like breathing muscles and also the heart muscle, but they would often live into at least the teenage years or into early adulthood. It, again, a devastating disorder, may be a little bit more common than SMA, affecting about 1 in 4,000 boys.

Host: And how is it diagnosed?

Dr. David Toupin: It is diagnosed clinically. And so, there is no newborn screening for Duchenne yet in the state of Kentucky, although it may be coming soon. It is diagnosed based upon the signs and symptoms, so a parent or a loved one will notice that their child is weaker, will seek medical care. And then, through clinical examination, blood work, and then genetic testing, the diagnosis is typically made.

Host: And what treatments are available for Duchenne?

Dr. David Toupin: Like SMA, it's a really exciting time for treatment in Duchenne. Previously, the only treatment was steroids, which would prolong the period of time that a child would be able to walk and may prolong life expectancy a little bit. There are new treatments that are out and soon to be coming out that may drastically change the landscape, hopefully, in a way similar to treatments have changed for DMD. So, there are new forms of steroids such as deflazacort and vamorolone. There is what's called exon-skipping therapy, which is a type of genetic therapy. And there are new versions of that coming out, which may have benefits. And then, in 2023, there was the first gene therapy that was developed called delandistrogene moxeparvovec or Elevidys. And that treatment may confer even more benefit than all the treatments before.

Host: Dr. Toupin, are all these treatments lifelong or does it treat it and then it goes away?

Dr. David Toupin: Great question. I'll start with just the gene therapy. So for SMA, the gene therapy for SMA, zolgensma, is thought to be lifelong. Now, we don't fully know that if the effect lasts an entire lifetime, because kids haven't lived long enough to tell that. But at least in the clinical trials, kids are now about nine, maybe 10 years of age, and they do not seem to be losing strength, the strength that they maintain from that treatment. So, it seems to have what we call a durable effect.

Now, the jury is still very much out on whether the gene therapies for Duchenne muscular dystrophy are going to have that same longevity. And that's just due to the nature of the cells that they're involved in and sort of how those cells work over time. So, the gene therapies are one-time treatments. I should have mentioned that. The other treatments like the steroids. And then, the other treatments for SMA, the nusinersen, and the risdiplam, those are treatments that have to be continued either daily or with periodic injections.

Host: And how is UK improving the care that they provide to people with Duchenne?

Dr. David Toupin: We are working very hard on this at the University of Kentucky. In my clinic, we offer something we call the NEMO Clinic, which is a group of providers, me, physical, occupational, speech therapy, and psychology. And we often do group evaluations together. We're working to build true multidisciplinary clinics where patients would be seen by not only our NEMO team, but also cardiologists, pulmonologists, endocrinologists, and others all at the same visit. And so, we're working to develop this at this time. But I can already say that if a family has concern that their child has one of these conditions, they can reach out and get a clinic visit with me and the NEMO therapists very quickly, to potentially make the diagnosis and start treatment as soon as possible.

Host: Is there anything else you'd like to add in closing that you think people might need to know?

Dr. David Toupin: I think the one take home-point from this is that for families who have been affected by these tragic diagnoses, there is hope. I think that's the main thing that keeps me going in this position, is knowing that there are treatments available or coming soon that are going to drastically change the lives of these children. And so, there is reason for hope. There's reason to come in and get care. There's reason to come get treated, because we can make a difference in their child's life.

Host: Isn't that the truth? Hope is the key when it comes to medical issues, especially with your children. Thank you so much for being here today and sharing your expertise.

Dr. David Toupin: Well, thank you. Thank you for having me.

Host: Again, that's Dr. David Toupin. To find out more, please visit our website at ukhealthcare.com. That's ukhealthcare.com. And if you found this podcast helpful, please share it on your social channels and check out our entire podcast library for topics of interest to you. I'm Maggie McKay. Thanks for listening to UK HealthCast, a podcast from UK HealthCare.