Philippa Cheetham, MBChB, MRCS, MD, FRCS:

® on “Spinal Muscular Atrophy: Physician and Patient Management.” Spinal muscular atrophy describes a group of disorders that are associated with spinal motor neuron loss. The age when symptoms begin correlates with the degree to which motor function is affected. Recent therapeutic advances have led to exciting treatment options for patients, which we’ll be talking about today.

I am your host, Dr Philippa Cheetham, an attending physician at Mt Sinai Hospital in New York and today I am joined by Dr Crystal Proud, a board-certified pediatric neuromuscular neurologist at the Children’s Hospital of the King’s Daughters in Norfolk, Virginia. And also with me today is Sebastian Mills, who is going to share the details of his journey with spinal muscular atrophy and subsequent treatment with novel therapies. Thank you so much for joining us today. Welcome, Dr Proud, welcome, Sebastian, welcome to 

®. Thank you so much for joining us today.

Crystal, we hear so much in the media about common diseases, cancer, heart disease, prevention, and educating patients about lifestyle issues. And yet, today, we’re talking about a disease that doesn’t get much attention. Many people have not even heard of this disease, spinal muscular atrophy. Can you tell us a little bit about this disease, how common it is, who’s affected by it?

Certainly. So, spinal muscular atrophy is a condition that leads to a deterioration of the motor nerves throughout the body. And it is actually something that impacts about 1 in 10,000 children that are born. The carrier frequency is actually reasonably high, so 1 in 40 to 1 in 60 individuals are carriers of this disease. And it’s autosomal recessive, meaning that it takes to partners who are carriers to have a child that could be impacted by this diagnosis.

 And in the title “spinal muscular atrophy,” we know it’s a medical term that means loss of. So, this is a diagnosis that affects the spine and the muscles. Can you elaborate a little bit more on how these patients present?

Certainly. So, it impacts the motor nerves which sit in the spine. They sit in the front area of the spine. They send out projections to the muscles. And so, 1 body says I’m going to make a movement in my arm, the brain tells his anterior horn cells that are sitting in the spinal cord send that signal out through that nerve and move the muscle. In the patients that have SMA [spinal muscular atrophy], the health of that motor nerves it in spinal column deteriorates over time. In the reason for that is because these patients have a missing or mutated gene called the 

 gene and that gene is responsible for making the protein throughout the body that keeps these motor nerves healthy.

 Now you’ve already mentioned that this is a genetic disease. It’s an inherited disease. And yet, 1 in 10,000, it’s not very rare but it’s also not a common disease. Is this something that can be routinely screened for? Is this something that families may be aware that it runs in the families? I mean, how we start evaluating, identifying these cases early on?

That’s a really great question. So with some of the newer data that we have available about early treatment, which we’ll talk about more, we know that there is advantage to diagnosing and treating earlier. And so, many states are moving towards doing what’s called “uniform newborn screening.” So, every child that would be born in a particular state would be screened, evaluating whether or not they were impacted genetically by this diagnosis of SMA.

The states that do not have that up and running just yet would have children that would present throughout either infancy up into later childhood with things like weakness, loss of motor function over time, or failure to meet those expected motor milestones that we would typically see in childhood.

 Right and you’ve already mentioned that this is a neurological disease. And there are many rare neurological diseases that primary care doctors may not see so commonly. Obviously, you’re a specialist working in this field who has seen these kinds of patients all day, every day. But, I would expect that some of the initial presentations are quite vague. And I guess a lot of patients present quite late after some of the warning signs that may be obvious to an expert like you may get missed by community pediatric doctors or primary care doctors. Is that what happens often?

That’s incredibly true. The journey to diagnosis can be very long for some of our patients. I think that most people when going to medical school, hear about spinal muscular atrophy, they hear about the typical infant presentation, which is usually around the age of 3 to 6 months and infants comes in, is a floppy baby of 4 years had control, a weak cry, does not reach the ability to roll over or to sit up.

And those babies, I think, are a little bit more recognizable but still sometimes go unrecognized or recognized too late. It’s not uncommon for them to be sent to physical therapists and say “Well, let’s see if we can’t build that strength,” and probably the most appropriate thing would be to see the physical therapist to work on straight, but also see a neuromuscular specialist or a neurologist to be able to proceed with finding out why am I not meeting those milestones.

 Right, right, and of course, there’s a huge spectrum in children’s development, even in normal spectrum, and I guess not all parents have children that behave the same, especially if it’s a first born. These early delayed milestones may not be so obvious to somebody that’s had other children as well.

Exactly, so that’s where we rely on not only the lack of expected progression but loss. So many of the children that we see, no matter their age, will have lost the ability to do something or we’ll be having more trouble doing something that used to not be so hard. And there should be true red flags to be evaluated by a neurologist. I had a 9-month-old little girl who used to be able to crawl and was having more difficulty and began to actually lose the ability to crawl and then was becoming more unsteady with her sitting. That backtracking, that regression really should indicate that there is something greater that needs to be evaluated there.

 And I guess for many parents where they’re comparing development with other children, for some there may be a sense of denial that my child is actually doing OK but it may not be as obvious to other people who see that there’s quite a lack you come across that sometimes, that parents are in denial that their child is not meeting the milestones that they should be?

Absolutely. I think that there is a great optimism and hope. And we certainly perpetuate that in the clinic. But we also need to identify when there is a problem so that we can now intervene with a treatment. And so really, I consider this a true neurologic emergency. If this is on my list of possibilities—if this diagnosis is in my differential, I need to send testing quickly because treatment is going to need to be urgent.

Spinal Muscular Atrophy (SMA) Overview

Spinal muscular dystrophy can equally affect girls and boys and does not have any predilection for certain ethnic groups.

 So, you’ve already talked about how there’s a huge spectrum. We know that with this disease, the younger the child presents, usually the more severe the disorder. Can you tell us a little bit about the spectrum of spinal muscular atrophy?

Yes. So, we used to actually characterize people in terms of types. And we don’t so much utilize those types anymore. But historically, they were able to allow us to do a couple of days. They were able to allow us to provide prognosis to families so that they could prepare. And they allowed us to be able to characterize patients so that we could put them into opportunities for research because you want to obviously intervene with groups who are similar, and then look at outcomes. So historically, there were types I, II, and III that are the most commonly referred to types. And genetically, they are the same. Phenotypically, they are different, and I think the one that you’re referring to that it’s most commonly recognized is the type 1 babies that without treatment would essentially pass away definitively before the age of 2.

 Before we bring Sebastian into our discussions, can you tell me a little bit about how patients present to you? Obviously, parents can jump on the internet and read these huge lists of signs and symptoms. Do you get patients that are referred to you with a suspected diagnosis that turned out not to have spinal muscular atrophy and they have a whole load of potential other issues? Or for most people that you see, is the diagnosis pretty obvious that it’s already being missed by a number of months or years already? How do people present to you?

It’s kind of a mixed bag, to be honest. So in infants who are floppy and weak, with a poor cry, and minimal movement of their arms and legs, I think that by the time they see me, their pediatrician has recognized that there is something that is very worrisome here. And there is this significant disconnect where the brains of our patients with spinal muscular atrophy are very much intact and so, I have these bright-eyed young children that are cognitively and socially very on track.

And their bodies cannot keep up with them because this is affecting their motor nerves. And so there’s this disconnect there. And when I see that disconnect, it becomes very obvious that this is what we’re dealing with. That obviousness becomes less, so when you have older patients, and Sebastian will share his journey with us, but it can often go underrecognized in patients who have achieved the ability to sit on their own and stand on their own but may have a difference in the way that they accomplish those tasks.

And so that could indicate a number of different considerations for diagnosis that I also evaluate for. Is there a difference in the brain signals? Is this a CNS [central nervous system] problem? Is this a congenital myopathy? Is it a neuromuscular junction problem? And so the differential can be a little broader for our patients who are older.

 So for patients who come to you we hear a lot now about concerns with immunizations. There’s been a huge amount over the past 25 years written about autism and other medical problems like cerebral palsy. Do you find these kinds of diagnoses in the differential for patients that come to you? Or, is it completely a different set of symptoms?

It’s a completely different set of symptoms except to a neurologist. So, to a primary care person, they may see that someone is just not keeping up. In the questioner’s mind maybe, we’re dealing with cerebral palsy. And so that is where that referral to a neurologist really is incredibly helpful because we can parse out what is upper motor neuron dysfunction, which would be seen in cerebral palsy, and what is lower motor neuron dysfunction, which is seen in the peripheral nervous system, which is my area of expertise.

 And you talked about the effect on the nerves, the muscles. Is there a discrepancy between the upper limb? Do you find that certain muscles are more obviously affected or is this a sort of generic across-the-board any muscle can be affected?

So it’s important to keep in mind that any muscle can be affected. And I think that the most important thing to recognize is that it’s also not just muscles of the arms and legs but also the respiratory muscles as well. And so, we have ways of measuring their strength over time because it plays a huge role in the health of our patients. But if we’re purely looking at a physical examination, there does tend to also be a pattern whereby the lower limbs tend to be more significantly impacted than the upper limbs.

 So obviously walking and I guess when patients are slow to crawl will go from sitting to standing, that’s when you see the issues.

Typical SMA Presentation Upon Diagnosis

 We’ve heard from Dr Proud about how patients present with spinal muscular atrophy. Can you tell us about your story, about how you were diagnosed?

It all started when my parents took me to the beach and usually children, when the water comes up, you try to jump over top of the water. I wasn’t able to jump as high, so that was concerning to them. My mom did do a lot of research over the years. They believed, like Dr Proud said, it was something just developmentally, but after a while they noticed that it was getting worse, and then I started actually getting in trouble in school for not keeping up with the other kids during PE [physical education] time.

 And how old were you when there was for such suggestion that something might not be quite right?

I was 3 or 4 when my mom noticed it but when I started getting in trouble, I was about 9 years old, but also in elementary school, too, I was getting in a lot of trouble for not keeping up with the other kids.

 If you think back to when you were at school, do you remember being slower in the playground compared with your friends? Do you remember that?

I did notice that. Social relationships were a little weird because they didn’t understand how I could, at that age, have such big muscles but couldn’t do a lot of the things that came with the athletic aspect of school. So, it was a little uncomfortable but I have a good personality, so I was able to navigate around it. But it did kind of trouble me and it troubled my parents because they thought I was just kind of—at 1 point, they thought I was kidding around at school. But once they actually learned that, once they started noticing stuff themselves, they’re like no, there is something really wrong.

 And did you ever get any comments from teachers at school about not moving as quickly as you should?

Yes, I got written up especially when we did like the mile runs or anything with a fitness test, just because I used to play around in class. I will admit to that but they just thought I was just playing around and when I tried to explain it to them no, I really cannot do this to that extent, they just thought I was making up excuses, so.

 And we’ve heard a lot already about weakness of muscles and strength. Any other symptoms that come to mind in those early years, other than sort of weakness, not being able to keep up? You didn’t have any pain or anything? No, it was just weakness.

Well, earlier in my early years, I did have pain that came with tight quad muscles so that was in the beginning, and they thought that this was all there was. Once we get those loose, you do a little physical therapy, you’ll be fine, and then once they realize that even with their physical therapy, there was still something wrong, and I was still moving slower than the rest of the kids, then they started to do more research.

 So, at what age did your mom first seek medical help and end up in front of a pediatrician? Do you remember that?

I do not remember that quite but I know that I was first diagnosed, I believe from my chart at 9.

 So, can you tell us a little bit about when you first met Sebastian and how obvious it was to you at that point, whether this was the diagnosis, or was it when tests were done that confirmed your suspicions?

So we have a very unique way that we met, actually, it’s a fantastic story. So my partners who I’ve been practicing neurology for well over 20 years used to take care of Sebastian when he was a younger person. He had not been seen in the clinic for many years. And when there was the first FDA-approved treatment for spinal muscular atrophy, I had joined the practice. And given my specialty, knowing that this new treatment was available, we decided to do a chart search to see if I could identify that there were any patients who would be amenable to treatment.

His name came up and over time, we begin making phone calls and my nurse reached out to him and said, "We’d like you to come in to our neurology department for a follow-up visit. You haven’t been here in several years." And so I walked in and I have never met him before. And I said “Hi, my name is Dr Proud and I’m a neuromuscular specialist. Did you know that there was a treatment for your diagnosis?” And he said “No”. And I said, “Man, do you get on the internet?” And he said, “No, I tried to stay off.”

And I said, “Well, let’s talk.” And over the course of our visit, we reviewed the new therapy that was available to him. So, it was a unique meeting because he already carried the diagnosis and his molecular testing had been done to confirm that he did, in fact, have SMA [spinal muscular atrophy]. And then, his examination I did, and it followed the path of what I would expect for someone with his phenotype to have.

Sebastian's Story: Initial SMA Symptoms and Assessment

 So if you were picking up the phone to talk to a community neurologist to have a patient in their office and they said to you, “You know, I’m concerned that this patient may have this diagnosis,” what would be the questions that you would ask of a community neurologist to say, “Have you done this, have you done this, have you done this?” to get the preliminary work up to know that they’re on the right road to making that diagnosis, before they even get to you?

I think that first and foremost is listening to the patient. What Sebastian said to us was that it had become something that had been affecting his life. He was setting them apart from his peers. It was not only setting him apart, but it was getting worse over time. He was having more trouble. Once again, there is that feature of regression or loss of previously gained skills. At that point, when you have someone who was telling you that they have weakness in your visualizing a degree of weakness in front of you, 1 of the first tests to do is a muscle enzyme test looking at CPK [creatine phosphokinase]. If it is elevated into the multiple thousands, 15,000 to 20,000, that indicates constant muscle breakdown from a process like muscular dystrophy.

 That was my next question. So, we’re going to be talking shortly about some of the specific treatments for spinal muscular atrophy. Now, for somebody who is not specializing in this area, we know that there are other neurological issues like muscular dystrophy. And yet, these treatments that were going to be talking about a very specific to spinal muscular atrophy and yet with other issues like Duchenne muscular dystrophy, I’m sure is a very similar presentation of these kinds of symptoms that patients present with, yes?

There are, and so it’s important to make sure that we’re kind of going down the right path. Are we dealing with muscles with dystrophy or nerve damage, and neurogenic abnormalities, which is SMA [spinal muscular atrophy]. So the CPK can be mildly elevated in our patients that have SMA but not to the degree that it would be for a dystrophy. So 1 test at least add to the list. And then these days, it’s actually incredibly easy to test for spinal muscular atrophy with no cost to the patient because all funding and support through various organizations, whereby that SMA testing can be done at no cost and returned within a week.

 And we’ve heard also about how Sebastian initially was getting physical therapy for tightness in his lower limbs. Is that a common presentation, that patients are going off down these other avenues and coming to you through not just through positions but through patients who have been taken care of by other support systems like physical therapy?

Absolutely. I really enjoy talking with my physical therapy and occupational therapy colleagues because they may actually see these patients before they see me. You know, it’s I think pretty typical for many doctors that, if you have weakness or if you have discomfort or tightness, I’m going to send you to PT [physical therapy] to see if I can make that better. And I think we need a little bit of a mind shift here where we can continue to try to make it better. But we also need to figure out the why. And I am where the “why”, hopefully, comes from.

So doing both at the same time is really what would urge these neurologists and primary care people.

 One of the things that I remember very clearly from medical student days doing pediatrics, is that you guys love to draw a family tree—brothers, sisters, mom, dad, cousins. You take value in asking questions about family tree to identify who may be the carrier where the other children in the family may be affected? How important is it to look at siblings like Sebastian and know whether there is other people in the family that may have an undiagnosed spinal muscular atrophy as well?

It is autosomal recessive and so it’s a little bit more difficult than if it were autosomal dominant. So, there are many, many families who have no other family member diagnosed with spinal muscular atrophy. And so the family tree, while in pediatrics, you’re right. We do consider that very important. So in the event that there’s no one else in the family with a muscle or nerve condition, it does not mean that this is not SMA.

 And you talked about the inheritance, the autosomal recessive vs. autosomal dominant. Can you drill down on what that means for the layperson when you’re explaining to mom and dad about the inheritance of this disorder, particularly for parents for thinking about the children? Can you explain what that means, autosomal recessive?

So, for Sebastian, it means that most likely his mom was a carrier. And as a carrier, you are not typically symptomatic so, mom would have no way of knowing that she was a carrier. She have no muscle weakness and otherwise would be a healthy individual. Dad was also likely a carrier and once again, asymptomatic, no way of identifying that he was a carrier. And those 2 individuals have a child who then has a 25% likelihood of having spinal muscular atrophy.

Dr. Proud, it always makes me smile when patients have a diagnosis without understanding treatment categories or disease categories. They always seem to want to know am I stage 1? Am I type III, type I mark? And yet often is not a clear understanding of what these different disease categories actually mean. As far as SMA is concerned, we’ve heard about type I, type II type III. How do you break it down and categorize the disease?

So these days, I actually do not categorize any longer. And the reason for that is because we’re in an era of treatment, where someone who used to be a type I is now defying that category. But I can refer to it in a historical sense. So we refer to someone as being a type I patient if they never reach the ability to sit. So, that’s going to be our infants with spinal muscular atrophy. Usually, they present with profound weakness in the first 6 months of life.

A type II patient reaches the ability to sit but never stands and walks. And then, our type III patients reached the ability to walk though many of them actually without treatment would lose that ability. And so Sebastian would be characterized, if I was characterizing him, as a type III patient who has the ability to walk.

 And you mentioned type III as the ability to walk. But it’s not like might walk or not walk. You find that patients and that type III category, some are walking but it’s delayed walking or they’re walking at the time they’re expected to but their posture may be different. Their balance may be different.

Absolutely. So Sebastian walked, in talking with his parents, at the time that one should, so he walked before the age of 1. But his parents noticed at about the age of 3 or by the age of 3 that there was a difference in the quality of his walk. And that is pretty characteristic of many of my patients, that even if no one else recognizes it visually, they feel different. They’re not the most athletic kid. They’ll have more tripping and falling, things like that.

As some of my patients who are categorized or would’ve been categorized as a type III patient, they actually lose the ability to walk and may need a wheelchair, even a power wheelchair to be able to move in the environment. And as we think about types, it’s critical to recognize that it’s a phenotype, that the DNA is the same across all of these phenotypes. All these patients have a missing or mutated 

 gene. They may have a different number of copies of that backup gene, which may help facilitate what that phenotype looks like.

Spinal Muscular Atrophy Diagnostic Workup

: You mentioned, Sebastian, that you had physical therapy initially, and then some time goes by before Dr Proud contacts you out of the blue and says, “Hey, I've got this new magic treatment.” How frustrating is it to hear that you had been plodding on doing physical therapy and then there's a lag before out of the blue, you hear about a new treatment? Could Sebastian have received treatment earlier, do you think?

You were in college. It was 2018, and this first approved medication was on December 23 of 2016, so a little over maybe a year and a half.

 How soon after hearing about this new treatment were you able to start it?

was a little apprehensive at first, honestly. I didn't believe it. I've been going this so long, and I don't believe this is going to work. But once I got home and I realized that it was taking a lot out of me to even pull myself off of the floor, I was like, “Okay, maybe I should try and at least see if this works.” So we went in, and it was my senior year, and we started trials.

 Did you feel at that point that you made any progress going through physical therapy, or not really?

I originally started physical therapy for the tight heel cord and the quadriceps. I made progress there. I had done water, I've done land, so I've done every type of physical therapy. I even had night splints. And I feel like I made some progress, but like I mentioned earlier, there was still something missing. So once I got to Dr Proud and she was like, “This is something that could probably boost all of that and help it from progressively getting worse,” I figured why not go ahead and give it a try once I noticed that I need to be optimistic about this situation.

 Now Dr Proud, we hear about new drugs coming out all the time for all sorts of diseases, and patients who have these rare disorders hear about a new drug and they're like, “Wow, this is the holy grail.” Do you have a huge spectrum in terms of response to these treatments when you have a patient with spinal muscular atrophy [SMA]? Can you give a predicted, this is what we'd expect, or is it still extremely variable patient to patient?

We know what the natural history of this disease implies. And so without treatment, I can clearly say and confidently say that if I gave Sebastian no medication, he would continue to have his motor nerves deteriorate over time and would reach a point where he would lose the ability to walk and would lose some of the motor neurons that help him to take a breath in and a breath out, leading to respiratory insufficiency. So without a doubt, I can say that progression and loss of function would happen with no treatment. With treatment, the world is our oyster.

And everyone is different, as you have mentioned. What we have seen from clinical trials and what I have seen in front of my eyes with the over 30 patients that we have on treatment at my center is, at a minimum, stability. And so when we talk about expectations in considering treatment, we talk about what our goals are. And my goal really is to maintain. Sebastian studied art, and I really wanted to make sure that those arm muscles that allowed him to do what he loved stayed strong, so that he could pursue a career and a family and wherever else life takes him. Stability really is my goal.

 Of course, nerves don't usually regenerate, do they?

 Once you've lost function, you're not going to be able to improve what's been lost. You're really just delaying further deterioration.

Well, to a degree. We've actually seen strengthening in our patients who have received treatment. It does not necessarily mean that that strengthening is coming from new nerves being regenerated because we know that physiologically, that's not possible. But we do believe that there are things happening at the cellular level, like a restructuring of the nerve where it's branching out to more muscles, perhaps strengthening at the neuromuscular junction. So, it's optimizing those nerves that are still present, that have not been lost.

 When you’re describing these novel treatments to somebody like Sebastian, how do you start the conversation in terms of explaining the mechanism of action and the condition, this is what we hope to achieve? And how do you monitor whether somebody is responding? Is it literally as simple as saying, “Look, they're walking better, the measuring of the strength of the muscles is better?” How do you assess that?

Oh, I wish it was that easy, but insurance really makes me do so much more. In starting the conversation, Sebastian may recall that I draw a lot of ugly pictures. Yes, I draw pictures of the brain, and then I draw an X, and I say, “Your brain is not impacted by this disease. You have a very smart, well-functioning brain,” as most of my patients do. And I draw the spinal cord, a little circle for where the motor nerves sit within the spinal cord, and then the projections out to the muscle.

And we talk about how that is the area where this disease impacts you. To understand how the treatments work, we have to talk about DNA. So, I talk a little bit about SMN1 gene and SMN2 gene. And that SMN1 gene is responsible in most people for producing that motor nerve protein that keeps those nerves healthy and connected to these muscles. There is a backup gene called the SMN2 gene, and that gene is a faulty gene.

It only produces that protein about 10% of the time. So in you and me, that may not matter that it's a faulty gene because we have that number 1 gene that's working well. But for Sebastian and patients with spinal muscular atrophy, he has a missing or mutated SMN1 gene. And so, his body is only relying on that backup SMN2 gene, and it's just not able to keep up with the protein needs that his motor nerves have.

 So you're trying to upregulate the protein with these novel therapies.

 I'm sure you get asked this question all the time in terms of regeneration of the nerves—stem cells. Is there any role for stem cell treatment in this disease?

I do, but we've got cooler things than stem cells.

 Sebastian, looking back now over the last 10 to 15 years, you’ve been on this journey with SMA since your early childhood. Looking back now and seeing where you are, do you see areas of your care when you think, “If only I could have gotten to this center, or I could have gotten this treatment?” Do you think there were significant delays in your treatment? Or if you could go back and start all over again, would you go down a different pathway to get better treatment, do you think? It seems like you had excellent treatment.

I obviously wish it was there when I first noticed the big jump in weakness, but everything happens the way it's supposed to happen. So, I'm glad I met Dr Proud, and I'm glad I'm able to experience this and be on this journey with her and getting to understand medicine not only for myself but people around me who will need it, too.

 What are the most challenging parts of having SMA for you right now? Are there some things that you want to do that you can't do?

 The weakness is the challenging point, but also that comes with the mentality of being able to know that you've got to push through it, too, and just trust that the medicine will do what it needs to do.

 On a daily basis, when you're busy with work and social life and just living, how much does your disease impact you? Have you learned to kind of get on with life?

 Or is it something you think about every day?

: I don't think about it as much as I used to. Like I said, I met Dr Proud when I was in college, so at that point, I kind of adapted mentally to it, that this is just something that I have and it's always going to be there. But at the same time, I think it's cool to think about it, too, at some point because it makes me want to be more open and express how I feel about it to other people. Even though I know it's there, and sometimes it gets on my nerves that it's there, I know it's a part of my life and I accept that. And then I also accept that there will be a time where I won't be worse off than I was.

 We hear often when experts are talking to other doctors at lectures, international conferences, you always hear these key points at the end of a presentation about how these are the patients we want to see. We want earlier diagnosis. We want earlier treatment. So often with these rare diseases, there's a delay in getting the right patient to the right doctor at the right time. What would be your key points in talking to non-experts in neurology about how to get patients to you, or to get patients to get the right treatment? How do we break down these barriers of delayed diagnosis? How do we do a better job as a medical community?

That's a great question. I think recognition is key. When you see weakness, and weakness that is progressive, even if it is slowly progressive. I have several of my colleagues in neurology who say to me, “But my patient with SMA is stable.” There is no such thing as stability and SMA. It is a constant deterioration of those motor nerves over time without treatment. And so recognizing that, I think, is the first key point.

There is no stability without treatment in SMA. Those patients need to have a discussion about options for treatment, even if they choose not to pursue that, and recognizing that this could potentially be a diagnosis in someone who's undiagnosed with this progressive weakness. Whether it is an older patient or an adult who was having tripping and falling episodes, or if it's a baby who is not meeting those motor milestones that would be expected, that is a time to pursue evaluation with a neurologist.

And a neurologist should keep this on their list of possibilities on their differential diagnosis. I consider it, like I said, a true neurologic emergency. Which is why my personal experience at my hospital is that if you call and say that, “I either have a patient with SMA that I'd like Dr Proud to see, or if I have SMA on my differential,” that patient is usually seen that day, the following day, or if they have to travel, I joke, as soon as they can get in the car and come down.

And I know many of my peers in neuromuscular neurology throughout the country feel very similarly. These are patients who we need to see quickly and institute treatment soon.

The Importance of Treating SMA Early

 Dr Proud, do you ever have the situation where you’ve got a patient you know is going to respond, who is the perfect candidate, but you are hit with a brick wall trying to get coverage? Some of these drugs are extremely expensive. Do you find that depending on a patient's insurance that you may not be able to get the drug as quickly as you want, or there's a lot of hurdles in getting coverage to start the medication as soon as possible?

You mentioned before some of the ways that we assess whether somebody is responding to treatment. And that actually is dictated by insurance. We're utilizing scales that were really created for research purposes, and now we've had to bring them into the clinic because of insurance mandates. And so we will do testing. I'm sure you love these clinic days where we put you through hours of testing.

My physical therapist and occupational therapist in clinic will perform things like the revised upper limb module, which looks at upper limb strength, and it gives a standard score. Something called the Hammersmith Functional Motor Scale Expanded, the HFMSE. We do that as well, which looks at all sorts of muscle strength—leg muscles, arm muscles, hip girdle muscles&mdash;and gives you once again a collective score. Those are 2 that are applicable to somebody who is Sebastian's age. And then, we have different scores for our children, our babies with things called the HINE [Hammersmith Infant Neurological Examination] and the CHOP INTEND [Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders]. And so we do that at baseline pretreatment, and then every 6 months. And we are mandated to do that to authorize and reauthorize these medications.

 Sure. Sebastian, you mentioned that you were in college when you first heard about this. Did that mean that you had to travel a long way to get treatment with Dr Proud, going to a center of excellence? Was it a real inconvenience to start off getting treatment?

Actually, no. I went to Hampton University, which is still within the area of Virginia, so I didn't have to go as far. But I know that Dr Proud said if I ever traveled outside of Virginia or moved, that there would be a way that I could still come back and still get the medication that I needed.

 The initial medications; we've heard that there are a number of treatment options on the horizon, and some are already being used regularly in clinical practice. There are obviously oral medications, and then we hear about therapies that are going directly into the spinal cord. Can you elaborate a little bit on the medications that Sebastian got and the form, the mode of delivery that those treatments took?

The first FDA approved treatment is nusinersen, or Spinraza, and that is a medication that acts on that backup gene that we were talking about. And what it does is it works on that SMN2 gene to improve production of the survival motor neuron protein. That's what Sebastian receives. It is the only one that is FDA approved for patients of his age. And it is an intrathecal infusion. And so, that means I deliver it through a spinal tap. And it's done in 2 phases, so the loading dose phase with administration on the first day of treatment, followed by another treatment 2 weeks later, then 2 weeks after that, 30 days later, and then every 4 months.

 Dr Proud is talking about this injection that you got into your spine.

 Had you had spinal taps before receiving this medication?

 When she first told you about receiving a medicine that was going directly into your spine, what did you think about that?

I don't know about that one,” but I said, “Well, we're already here. Let's go ahead and try,” but I was a little freaked. I have a bunch of tattoos, but something going into the spine was a little scary.

 You had that done in the office, did you?

Yes, she gives an option that she does a numbing creams, and then you can put ice on it. I'm starting to realize I like the ice a lot better because it does numb the area a lot more. And then from there, I’m kind of in a fetal position, and she goes ahead and gives me my infusion from there.

 How soon after getting the infusion did you start to notice some improvement in your symptoms?

People may not believe me, but the first time I got it, my legs were feeling warm. So I'm like okay, I think it's working.

Your parents called me the next day. They said he's outside washing the car.

I would say within the next couple of months, I did start to see a difference. I wasn't falling as much. Previously before getting my medication, I used to fall a lot. My leg or my knee would give out a lot. Now, I have a lot more strength. I'm able to do a lot more than I was able to do, as well as being able to drive. That was a big concern for my parents, losing that motor skill. I'm still able to drive. I still have some things that I'm working toward, but my strength is a lot better, to where it’s maintaining, so I don't end up hurting myself.

 How many injections have you received into the spine?

You’ve been on treatment since April 2018, so, many.

 What's the time frame between each infusion?

Now he goes every 4 months in the maintenance phase.

 And the dose for maintenance is a lower dose than the original doses?

No, it's actually all the same, which is interesting. And it's all the same no matter whether you're an adult or a baby.

Treatment Barriers: Cost, Location, and Delivery

 Obviously you managed to convince Sebastian to go for this in the office. How do you get around this for younger children who clearly aren’t going to be able to lie on a bed and have a spinal infusion?

They do amazingly well, let me tell you. For babies, their parents want this for them because obviously, they know that without treatment, they're going to lose their child. I think it becomes a totally different conversation when we're dealing with an infant. For my older patients, starting at the age of about 3, I think my patients really start having much more of a conversation about this. I've mentioned that the brain is not negatively impacted. My patients are very bright. And so my 3- and 4-year-old patients with SMA [spinal muscular atrophy] will tell me their opinions about what we're doing.

 On the day, do you always succeed in getting the patient to lie there to get the spinal tap? You never have to resort to sedation or anesthesia?

We started out with those 3- to 5-year-olds, trying some sedation. And what we found was that actually, our patients really did not like the IV [intravenous] placement for the sedating medicine. They preferred to be distracted. They will play music; as you know, we like to jam out a little bit. They can put on headphones. Many of them will play games on their phones, or they’ll watch TV through an iPad, or they'll watch a movie. Even the youngest patients tell me—3, 4, 5 years old&mdash;that they would really rather me just do a very quick spinal tap and get it done with, than have a bunch of IV pokes and medication, which can make you feel nauseous afterward. They don't want sedation. I do offer it if they would like it, though.

 It's amazing. We've heard about some of the real improvements that you can get from these treatments. When you’re counseling parents and children about the risk of these treatments, what do you discuss? Obviously, the procedure itself, a spinal tap, is not child's play. Do you consult patients about the risk of the tap and what the downsides are of having these infusions?

Yes, absolutely. We talk about both the lumbar puncture risks and the risks of medication. With the lumbar puncture, we talk about things like infection, which is why it's done as a sterile technique. We talk about the risk technically of bleeding, since I'm puncturing the skin, although I reassure them that the area that I'm going in is not highly vascular. We talk about the risk for post lumbar puncture headache.

Although, I use an extremely small needle; I use a 22 gauge for most of my patients. And I'm reasonably good at what I do, so there is not a whole lot of wiggling around, which would leave a big tear in the dura mater, which usually is the culprit of those spinal headaches. My spinal headache incidence is incredibly low at this point.

 After the spinal taps, were you straight back to normal living, or was there a period of 24 hours, 48 hours where you had to take it easy?

The first time, I did have a little bit of soreness. But after that, once you get it, it's just like, “All right, I'm going to work.”

Most of my patients will say, “I've got to get back to school.”

 You never had any problems with headaches or any symptoms other than just local irritation from where the injection was?

Yes, personally, I haven't had any symptoms. It was just, as you said, the lower irritation the first or second time. That's about it.

 Now we've heard that this disease is not common. When you're treating patients like Sebastian, who is a great advocate for other patients who have been through these kind of treatments, do you get patients to talk to each other, to be advocates? Do you use people like Sebastian to egg on other patients to get treatment?

HIPAA [Heath Insurance Portability and Accountability Act] kind of prevents me from doing that, although it is an incredibly small community. We actually have a Muscular Dystrophy Association clinic, and there’s a Muscular Dystrophy Association camp. Did you ever go to camp? I don't remember.

You need to go back to camp. Several of my patients actually knew each other from camp days. And so I would encourage them to reach out to each other, but I'm not technically allowed to connect patients 1-to-1. Although I'm really fortunate that groups like Cure SMA, and there are some local Facebook groups that have allowed for a community to come together and to get corroboration about experiences through diagnosis and treatment, so that's been helpful.

 Sebastian, we know that this is not a common disease, and yet, when you're talking to specialists like Dr Proud, it's what she does all day every day. What's it like when you talk to other doctors who don't have the knowledge about this disease? Do you find that you're having to educate them on what's actually been going on with you?

I would say yes, and I think Dr Proud is awesome with that. She gives you the rundown of everything, so when you do come to people who you need to have the dialogue with and explain stuff to, it's easier for them to understand and be able to know where to navigate their research toward.

 And to bring you back into the discussion, for patients like Sebastian who are interacting with doctors maybe through college, they're a long way from home. They're potentially a long way from a center of excellence. Do you give them advice on, “If you see other doctors, these are the kind of things that you need to warn them about?”

Absolutely. So some of the things that you just alluded to, respiratory care is incredibly important. We know that the recommendation is that these patients receive their annual influenza vaccine. We give that in my clinic, but if for some reason they're not due in clinic during the season, then I would recommend that they receive that at their primary care doctor visit, and also that they stay up to date on all of the other routine vaccinations to prevent as much preventable disease as we possibly can, since they're at higher risk of hospitalization if one of these diagnoses impacts them.

Flu and pneumonia are incredibly different in a patient with SMA than in someone who does not have SMA and can actually land them in the hospital in the intensive care unit. And then, likewise, when we're thinking about respiratory insufficiency and the risks that go along with it, making sure that if a patient has something that takes them either to the emergency department for emergency surgery or even for a scheduled surgery, that they need to be advocates to speak to their anesthesiologist and say, “Hey, I have a motor nerve disease,” because that anesthesiologist may have a very different approach, pharmacologically with them than they would someone else.

Treating Children and Spinal Tap Risks

 Now these medications are going into the spinal canal. Are there systemic effects that may have effects on liver function, kidney function, or general immune function that patients need to be aware of?

Spinraza has some FDA recommended analyses that should be performed prior to using it for treatment, and then with each successive infusion of medication. We perform blood and urine tests. We check a complete blood count, a PT [prothrombin time], a PTT [partial thromboplastin time], and a urine quantitative protein. Some of those recommended evaluations are because Spinraza is considered what’s called an antisense oligonucleotide, an ASO. And there are other medications that are ASOs that have been demonstrated to have certain adverse effects. And so as a class result from ASOs, the FDA has recommended that we check those things. We do that routinely for our patients. I personally have not had any patient who has had any of those adverse effects, but we continue to follow FDA guidelines and check those.

 Sebastian, when you first heard about this treatment, did you think that these infusions were just going to be a one-off and you'd be much better? Were you aware that it was going to be an ongoing process where you'd be having these top-up infusions?

 Yes, Dr Proud did explain how the maintenance and all of the loading actually works. Of course, with anything, your body has to adjust to it. So, the 2-week trials, and then you go from the month to the 4 months; she did explain that to me very well. I did understand this will be an ongoing process, but I also understood that through this ongoing process, you won't see stuff overnight. With the testing that usually occurs after all of my shots, I'm able to see whether stuff has gone up or it's at an average level now or if it's staying in a consistent basis.

 One thing that I really wanted to clarify, when you see a patient upfront with spinal muscular atrophy, and you’re planning treatment, do you modify the frequency of these infusions based on response? Or do you have a set protocol where you want to say, “Look, we’re going to give infusions at this time, this time, this time, this time, regardless of whether you have a good response or not. And then at the end, we'll evaluate.” How much does the patient response throughout treatment dictate the frequency and the number of infusions that you're going to give?

There is a set routine, a set frequency that is in the prescribing information, so I am not permitted to move it forward or backward. It is set at every 4 months and maintenance. However, there is the discussion that goes into the planning phase, which I think you're referring to. That discussion becomes much different with a patient who, in the past, would have been labeled a type 3, like Sebastian.

When we see our type 1 and 2 babies who are declining in front of our eyes quite rapidly, their response to treatment can be very readily visible within the first few months. Our patients who are older and who walk, like Sebastian, we know are already starting with a higher baseline number of motor nerves that are present and that we may not see as dramatic of a response as rapidly as some of those younger children, but we do still see a response. It just may be that we need a longer commitment to be able to observe and quantify that.

And so, I ask my patients up front that I would really like a commitment if we are going to move forward with this treatment together. I want a commitment that we're going to pursue this and really obtain some objective data before hearing someone say, “I don't think it's doing anything for me, doctor.” Usually, I ask for somewhere around 1 or 2 years to be able to look at scores, look at tolerability, look at comfort level and see whether we've achieved something that's desirable to the patient. And I've not had anyone come off of treatment after that period.

Systemic Effect Prevention: Evaluation & Dose Modification

 Sebastian, I have 2 questions for you. We know that as the day goes on, we all get tired, and muscles get weaker as the day goes on. Do you notice that certain times of the day are better for you, that you have more energy in the morning? Or does it not really work like that? Do you have good days, bad days? Do you have parts of the day that are better for you than others?

Yes, I have good days and bad days. I was previously working with children, small ones at that, so trying to keep up with them was a little difficult, but being able to receive my spinal infusion has it made a lot better. I did notice though, I still do have some weakness, but it's gotten a lot stronger. And especially with children, being able to pick them up was a big thing for me because some kids you have to change and stuff like that, and I did notice that my arms were a lot stronger as well. So I would say there is no real difference for me. Maybe during the wintertime when muscles are a little stiffer, that's about it. That’s when I noticed there is some stiffness, but other than that, it's been at a consistent level for me.

 When you're coming up to having an infusion and a few months have gone by since the last infusion, do you start to feel like, “Yes, I'm ready for a top up.” Do you notice it weaning off?

I did explain that to Dr Proud a couple of times I've been back that I felt my body knows that there is an adjustment that needs to be made again. I don't feel actual weakness, but it’s a difference in my body when I know my shot is supposed to be coming up.

 When you have patients going through these treatments, what percentage of patients would you say don’t continue to receive maintenance therapy because they’re just not showing the kind of response that you’re looking for? When do you decide, “You know what, this treatment is not working. We're going to pull the plug and go on to something else.”

I've not had anybody discontinue treatment. And actually, nationally, there’s an incredibly high adherence rate to therapy. More than 95% of patients who have started have stayed on it. I hope that our patients will continue to commit to ongoing therapies. And for something that sounds so different than taking something orally, that having to come in and commit to a lumbar puncture every 4 months, I like to think that my patients are recognizing these differences that it's making for  them to commit to such a procedure. And his score has dramatically improved on his standardized testing from his pretreatment numbers. So I've got objective data. And I'm not the person who's scoring that. That's my physical therapist, who is incredibly rigorous at the testing that she does. He can tell you that. She's very strict.

 You don't find any evidence that patients, with time, are becoming tolerant to the infusion?

 The success rate really is phenomenally high, isn't it?

 Now, when would you consider changing treatment? We have these other treatments that are being reported as having success as well. Where's the future in spinal muscular atrophy [SMA] in terms of new treatments on the horizon? Can we do any better than we're already doing?

Absolutely. I am thrilled to be at a center that participates in clinical research trials. And actually, the question that I would ask would be a little bit modified rather than when would we switch someone, but when could we add? I really see SMA in the future as being a cocktail approach, where we are providing a number of different interventions that work at different levels and different locations. There is right now only 1 FDA approved treatment for spinal muscular atrophy in patients who are Sebastian's age. Spinraza is approved for all phenotypes and all ages because of its mechanism of action. Whether you're a child or an adult, you have SMN2 genes, and that's where Spinraza acts. The other FDA approved medication is only indicated for children under age 2 and that is onasemnogene abeparvovec which is commonly referred to as Zolgensma. That is a gene replacement therapy. So, it works differently.

It is, it was just approved in May 2019. It actually serves to infuse what's called a transgene, which is supposed to replace that missing SMN1 gene, to once again produce that protein that's missing.

 We've talked earlier about progressiveness of this disease, that often there's a very slow stepwise deterioration. Do you find that some patients have a waxing and waning, where some days may be much better or some weeks and months may be much better, where it's not quite so obvious that there's a problem? And then, there may be a deterioration that kind of flip flops. Or is it always this very gradual step-by-step loss of muscle tone and power?

It's usually that gradual progression, and actually, so much so that most of my patients would say they don't recognize it until they look back, right? And they think, “Well, 5 years ago, what could I do then that I can't do now?” And it's not until you ask some of those questions that you pull some of that loss out. And obviously, we don't like to focus on losses. But it is an insidious thing. It's very slow and progressive. Now in babies, it may be a little bit different.

It may be more dramatic because it happens sometimes much more quickly, so that change becomes more readily apparent over time. The waxing and waning doesn't tend to happen so much just from the disease itself. But we can see a difference in the body's strength as it relates to things like recovery from illness or injury. So, if one of my patients falls and has a fracture, that may actually end their ability to walk because their ability to recover from that injury may be significantly impaired. Being hospitalized for pneumonia may actually set them back more significantly from a broader perspective than just from their disease alone, because of the need to compensate for that illness.

 We've talked a lot about the musculoskeletal effects and walking, delayed milestones, delayed sitting. But these other presentations may not be so obvious to people who aren't experts. We’ve talked about the pulmonary complications and the nutrition, the GI [gastrointestinal] complications that may not ring the alarm bells as early as a child who’s slow to sit or slow to stand. You see that as well, yes?

Life During Therapy: Good Days and Bad Days

 Now we've heard about all these novel therapies that were available with astounding success. Obviously, you're not working in isolation. You're working as a multidisciplinary team. How do you work with physical therapists to optimize the improvement that you can see in building muscle strength with exercise, lifestyle? What advice do you give to patients to maximize the performance outcome from this boosted muscle function?

Sebastian can tell you we have incredibly rigorous clinical days, so when he comes for an appointment, how long do you think you're there? Two hours?

Yes, that's true. He's chatty. So, probably a minimum 2 hour appointments, and that's because of this multidisciplinary team that you've referred to. A physical medicine and rehabilitation specialist is present, a physical therapist, occupational therapist, respiratory therapists, we’re monitoring spirometry measurements. We have an SMA [spinal muscular atrophy] dietitian in clinic because nutrition is so incredibly important. We have a social worker, an educational liaison who helps us communicate the needs of our patients to schools. We have a variety of different individuals, including my nurse coordinators, who help to try to make it so that medical appointments do not become your life, that we can try and consolidate to the best that we can. And so, it really is an incredible team approach to be able to maintain and optimize the lives of our patients.

 You've talked about nutrition. Can you elaborate a little bit on the role of nutrition, diet, lifestyle in the management of this disease because we're talking about muscle function? What kind of advice do you give patients in terms of nutrition? And why is nutrition such a big problem for patients with this disease?

Right now, there is not a clinically or a scientifically tested diet that is technically recommended. There is still more research that needs to be done into that. But nutrition is incredibly important for patients with SMA. We find that with our younger children, they may be at risk of what's called failure to thrive, where they cannot gain appropriate weight. And that's probably because they're working so hard to keep up with others that their metabolism is just incredibly hard and incredibly high within their muscles. We see that the opposite may happen, actually, in our adult patients, where it may be difficult for them to lose weight, especially if they have limited mobility. For my patients who cannot walk and are utilizing wheelchairs and power wheelchairs, their ability to burn calories is so very different. And so, they may be at risk of being overweight. My nutritionist really has to span that entire gap and be able to help to supplement the needs of our kids with failure to thrive and then be able to help try to modify some of the diets of our older patients who may be at risk of being overweight.

 Sebastian, do you feel kind of isolated, having had a diagnosis that's quite a rare diagnosis that most people have never heard of? Does that make you feel nervous when you talk to other doctors who may go, “Oh, I don't even know what that is, or I've not heard of it?”

In the beginning, it did because I honestly didn't know anybody else who had it. But through Dr Proud, they were able to put these groups together where you're able to meet people even of your age who have the same diagnosis. You're able to form bonds and relationships and actually talk about things that you might not have been able to talk about before. And when you go see these doctors, now you're able not only to be more educated because of what Dr Proud has told me, but also become more comfortable having conversations about it.

 Right, and now with access to the internet and social media, are you a member of any SMA groups, or are there any particular websites or resources that you think are helpful for parents and families who may be starting off on this journey looking into treatment options for spinal muscular atrophy?

Yes, I know you can look SMA up, as well as go to the website.

Yes, there's a CureSMA.org website, and it gives you a bunch of information. And even when you see Dr Proud for the first time, she gives you a pamphlet, and a packet, and a booklet—she gives you a lot of information as well. And there's actually a kit, too, that comes with everything that breaks it down. Like she said, her pictures that she draws that break it down, it gives you a bunch of information to take in and be able to understand and communicate, “Okay, from now on, I know what steps we need to take.”

Absolutely. The largest resource comes in the form of CureSMA. That is the organization that supports patients and families impacted by spinal muscular atrophy. And there's an annual conference, both for patients, families, caregivers, and clinicians every year. There is a website dedicated to this organization, CureSMA.org. It has resources for families. It has resources for diagnosis. It has identified areas where treatment is being offered. And it will actually keep people updated on some of the new treatments that may be coming available in the future and research opportunities. So it's a great resource for anyone.

Multidisciplinary Management and Educational Support

 Do you see the potential red flags in terms of decade of life, that as Sebastian gets older, you may have other concerns of the effect of the diagnosis on medical issues that he may have in the future?

We don't necessarily see that this impacts other organ systems in a different way than it would in somebody who is typically developing. It is incredibly important to make sure that our younger patients who will be surviving into their 60s, 70s, and 80s, continue to seek routine medical care that's appropriate. That can be very difficult. It can be hard for some of our patients to be able to get onto an examination table to perform things that are recommended, like a colonoscopy, or women getting their yearly examinations. And so I really try to reinforce to my patients that as uncomfortable as it may be, you need to keep up with the routine standards of care because my hope and expectation is that you will live a very long and fruitful and healthy life.

 Sebastian is now 22. Do you have questions about how to screen your own children in the future and what tasks need to be done? How do you broach those subjects when you have a patient with SMA [spinal muscular atrophy] who is asking about their own family?

I'm actually 23, but it's fine, they won't check my ID as much. But we did actually just talk about this. We talked about how, whoever I decide to be a partner with, they'll be able to do the scanning there as well, and to see the potential of the child having a baby as well. There's also research, I believe that you said that they could see which eggs would actually have the SMA gene and the ones that don't have the SMA gene. There are a lot of things in science now that are becoming very beneficial to people with SMA to try to move forward and have those families and be able to know how to take care of the child when the child comes into the world.

 Would you be recommending genetic testing early on in this situation?

The American College of Obstetricians and Gynecologists now recommends that individuals be tested for carrier status. We know that Sebastian is affected by spinal muscular atrophy. The next question is whether his partner would be impacted as well. And so, we would then test that partner to say whether they were a carrier. If that individual was a carrier, we would know that there would be a risk to the future offspring, that they may be impacted by the disease itself versus being carriers themselves.

And so, we would approach that very differently. We do have a genetic counselor I work with who is able to help us educate our individuals who are looking at family planning, or families who already have a child who was impacted by SMA and who might want more children in the future. And how do we go about that? There are options these days, which Sebastian was alluding to, with consideration of things like in vitro fertilization with preimplantation genetic diagnosis, called PGD, that can identify embryos impacted by SMA and those that are not. So we have a whole world of things that need to be discussed when we're talking about family options.

 Sebastian, we've heard that you have a phenomenal medical team around you, and you’ve had access to novel therapies, where it's actually very proactive that you got this infusion up front, where Dr Proud reached out to you at college. Who else has helped you on your journey, other than the medical profession?

My parents. They're awesome. They're very supportive. Especially my mom, she pushed me into it. She guilted me into doing it. I'm glad she did because if not, I probably would have been, like I mentioned earlier, worse off and still having trouble picking myself up off of the floor. I do still need assistance here and there, but I'm getting a lot stronger each day and especially when I get my infusions, they're helping a lot, so I'm grateful.

 When you're with peers at college and friends, do they have an understanding of the effect of the disease, do you think, on your limitations? Or does it not really come up in conversation?

do. It's to the point where if somebody is staring at me, they’re defensive about it because they understand what's going on. Actually, I've educated the people around me enough to where they can educate somebody else because sometimes there's a side conversation when people are uncomfortable to come to the person. So I've educated the people around me enough for them to be able to explain to somebody else, that it’s okay they’ve never heard of it. It's always good to get the information out there to everybody, even people who may not have heard of it or even know what it is.

Family Planning for People With SMA

 We have to strike a balance between patients getting the best possible care in a center of excellence versus the inconvenience of travel and how far away an individual family may be from an expert like yourself. And obviously, it's not a 1-size-fits-all. But do you advocate that all patients with spinal muscular atrophy [SMA] should be coming to somebody like you and accepting that there's a big inconvenience factor in traveling, but the trade-off is they’re going to get better care?

Or do you think that we need to do more to educate community neurologists to do a better job for patients closer to home? What do you think is the ideal way to manage patients with spinal muscular atrophy so that they get the best possible care without all the inconvenience of trying to travel miles and miles to see somebody who may not be on their doorstep?

And we do. We have patients who travel from many states away to come to our center, and we’re very fortunate that they find benefit in that. I think that we need to strike a new interest in the subspecialties of neuromuscular neurology. And so my hope is that medical students who rotate with me will see the enthusiasm that we have in this field and will go into neuromuscular neurology in the future.

I do believe that every patient with spinal muscular atrophy deserves to see a neuromuscular neurology expert. I think they deserve that comprehensive care that comes along with a center that has experience in not only treatment options but the other multidisciplinary care that is necessary to be able to optimize these patients’ lives.

So even if it is not where they receive their treatment routinely, I think it really would benefit every patient to go to a center of excellence for consultation on some frequency, to be able to follow up and make sure that they are keeping up with the standards of care for SMA and also that they're able to participate in new and exciting research. The job is not done.

We have 2 FDA approved treatments but we have more, hopefully, that will be coming, and we want to be able to offer this to all of our patients. Everyone deserves the opportunity for treatment. Everyone deserves the opportunity to participate in a clinical trial, if that is within their wish and within their choosing.

Spinal Muscular Atrophy (SMA): Physician and Patient Management

Spinal Muscular Atrophy (SMA) Overview

Typical SMA Presentation Upon Diagnosis

Sebastian's Story: Initial SMA Symptoms and Assessment

Spinal Muscular Atrophy Diagnostic Workup

The Importance of Treating SMA Early

Treatment Barriers: Cost, Location, and Delivery

Treating Children and Spinal Tap Risks

Systemic Effect Prevention: Evaluation & Dose Modification

Life During Therapy: Good Days and Bad Days

Multidisciplinary Management and Educational Support

Family Planning for People With SMA

Centers of Excellence and Future Oral Medication

Psychological Effects of SMA on Children and Adults

The Impact of the ENDEAR Trial Regimen

Ongoing Clinical Trials & Managing Patient Expectations

Adopting Neuromuscular Therapies for SMA