 SMA, or spinal muscular atrophy, is a gradually progressive motor neuron disease. It’s a genetic motor neuron disease. The classical model of motor neuron disease that we know about is Lou Gehrig disease, or ALS [amyotrophic lateral sclerosis]. Spinal muscular atrophy is very different from that. It’s not the same disease. But it does involve the gradual loss of motor neuron function. The other functions—sensory, as well as cognitive function&mdash;are very well preserved. SMA is a genetic disease that begins at birth. Patients gradually lose motor function abilities. This includes walking. In some kids, it can involve their speech. It can involve breathing and swallowing, but mostly the arms and the legs are involved.

Spinal muscular atrophy is a genetic disease. The primary cause is a genetic mutation in the survival motor neuron—SMN. The mechanism typically involves a deletion of 

, which is the primary survival motor neuron. There is a little second side copy of it, 

. But, that 1% difference means it minimally functions as an SMN protein.

So you’ve got a copy of gene that’s barely functional, and you’ve got the major copy. If that copy is deleted, patients will go on and develop spinal muscular atrophy. Some patients have multiple copies of this 

. If you get 3, 4, or 5 copies, that little bit of function of 

 all of a sudden becomes enough so the nerves can function and survive. That’s why we have different types of SMA. We’ll talk about type 1, type 2, type 3, and type 4. The type of SMA depends how much 

SMA is present in about 1 in every 11,000 births. What’s interesting is about 1 in 50 people are carriers for the disease. The actual genetic mutation that I’m talking about is present in about 1 in 50 people, but because it’s what we call recessive, you have to get a mutation from mom and from dad to get the disease. So that’s why it’s only present in about 1 in every 11,000 people. The people in the other group—the other 1 in 50&mdash;are perfectly normal. They may have 1 mutated gene, but they’re got 1 perfectly normal 

and that’s enough to provide normal function so they can live life fully and do well.

SMA is a progressive motor neuron disease, that is gradual loss of the motor function. The way it can typically present is with weakness in the bigger muscles, or the more proximal muscles—the hip girdle, the shoulder girdle. You could see a gradual loss in function of some of these muscles. The way SMA will present depends on how old you are. Some of the pediatric patients, or some of the infant cases, the type 1 SMAs, will present with weakness very early in life. They won’t be able to sit up. They’ll have difficulty rolling. If the disease is severe enough, and if it involves their mouth and their ability to swallow, they may have difficulty suckling. They may start presenting with normal milestones, and then they start losing those.

Now, if we look at the type 2 and type 3 patients who present at 6 months, 1 year, or 2 years, again, they start making more of those milestones, but then they start losing milestones. When we get into the later onset and some of the type 3 and type 4 cases, or when they present with the disease after age 18, some of these patients will have normal lifespans. They may not be the best athletes. They may be slow and clumsy. They may have some mild proximal weakness that may present later in life and become a problem. Some patients present with tremors. They can present in many different ways, but they all have the same pattern of this gradually progressive weakness. It just depends on the type—how early and how severe is it going to present?

Overview of Spinal Muscular Atrophy

: The current classification includes 4 phenotypes with a large heterogeneity of the symptoms of the disease. On 1 end of the spectrum, we have the more severely affected infants. Those are SMA [spinal muscular atrophy] type 1 patients with a heavy involvement of ventilation of the phrenic-innervated muscles. On the other end of the spectrum, we have patients with SMA types 3 or 4, with a minor involvement of the muscles of the extremities. Especially in the SMA type 3 population, there is a large heterogeneity. We have patients who lose their status of ambulation within their first years of life, and on the other hand, we have some patients who are still able to walk in their 40s, so there is a large heterogeneity.  

Within the last several years, we doubt the existence of an SMA type 4. When you ask these SMA type 4 patients, who you may think only had involvement after reaching adulthood, you can see that there are always minor symptoms within their adolescent years. The patients who are now classified as SMA type 4 have minor forms of SMA type 3. 

The spectrum of the disease is largely heterogeneous in severity. A severely impaired patient with early problems who needs mechanical ventilation within their first years of life is on 1 end. On the other end of the spectrum are patients with only minor involvement of extremities who have minor problems when climbing stairs or performing activities like that. That is the spectrum of the disease. 

Spectrum of SMA Phenotypes at Presentation

: Genetic testing is the basis of diagnosis for type 2 SMA [spinal muscular atrophy]. In the years before drugs like nusinersen were available, genetic testing was not performed in every case, especially when patients had a long-term diagnosis. At that time, genetic testing had no consequence on treatment. Often, a diagnosis was made by symptoms, in addition to some electrophysiologic diagnostics. Now that treatment is available, we need the confirmation that it’s really a 5q SMA. 

The classical test is the multiplex ligation-dependent probe amplification, or MLPA, to detect the deletion of the SMN gene, and to detect the copy number of the SMN2 gene. Besides that, a classical test can also be performed from a dried-spot blood test. Those are the common tests available. 

In most cases, you have homozygous deletion of the SMN1 gene, but there are a few cases that are compound heterozygous. We have a deletion on 1 allele of the SMN1 gene and a point mutation on the other allele. The SMN2 copy number determines the severity of the disease. There is a good correlation between increasing copy number and a less severely impaired patient. Typically you have, for example, 2 SMN2 copies in an SMA type 2 patient, and 4 SMN2 copies in an SMA type 3 patient. This is a correlation in approximately 80% to 90%. There are also other patients in which you don’t have that correlation. We possibly have some other genetic modifiers. 

Genetic Testing in SMA

: The term later-onset disease is a bit wrong because these are genetic diseases. By their very nature, they start when you’re born and are present your whole life. It’s just that in later-onset disease, you have enough spare copies of the gene so you can delay that onset until later in life. Again, when you have more copies, it’s going to be slower and gradual in its decline. You’re still going to get the same presentation. That is, the weakness in the muscle, difficulty running, and difficulty getting up the stairs.  

You may have problems reaching something on the top shelf in your kitchen cabinet because of shoulder weakness. It will present more with that. It will be milder. They’re less likely to have as much of the swallowing or speech changes as someone who’s younger. But these things can be there, and they can be disabling and need to be treated. 

The age and onset is a function of the type. We had talked about the type 1 patients who can present at birth. In type 2 disease, you start seeing it at 6 months. When you start getting to the type 3s and 4s, they can present as late as 16 or 20 years of age. There are some patients who have been reported to present at 30 or 40 years old with type 4 disease, where they have enough of the SMN2 that it can compensate and it doesn’t occur later in life. These patients can present at any age with SMA [spinal muscular atrophy]. When it presents earlier, it means it’s more severe. 

Tim Hagenacker, MD: The later the symptoms occur, the broader the differential diagnosis. You have other motor neuron diseases, like familial forms of amyotrophic lateral sclerosis, which has to be considered when proximal tetraparesis occurs. On the other hand, in the early onset forms, you also have to think about congenital myopathies, which may have similar symptoms. That’s the reason why the genetic testing is so important. 

For an experienced child neurologist, diagnosis is typically not that difficult, because during childhood, SMA is 1 of the most common forms of neuromuscular disease, especially when severe tetraparesis occurs. During adulthood, it can take some time—probably years&mdash;If patients don’t have access to a neuromuscular expert center. 

Considerations When Diagnosing SMA

: There are 2 types of motor testing that we’re going to do. The first thing we do to assess disease is listen to the patients. What can they do? What can’t they do? If they have difficulty going up stairs, that suggests a proximal weakness. It may be difficult to get out of a car or a deep seat. When we go through and do the physical testing for the motor patients, we will focus on what we see in the strength test. We have a scale that we use that’s from 0, meaning no strength, to 5, meaning normal strength. We look at where they are on that scale in terms of their strength, and we see if there’s any relative weakness that’s involved.

For the infants and kids who have this, we also have other functional scales. We have the Hammersmith Functional Motor Scale. We have different write-up or Revised Upper Limb Module. We have different scales that look at the developmental milestones patients are supposed to reach. In some of these patients, as you monitor it you will look at whether they are able to sit up or roll over. Those motor scales for the pediatric patients tend to be more functional. What can they do? When you get into the adults or the older kids that can cooperate, instead of just doing that, you’re actually scoring how strong the muscle is on that 5-point scale.

The decline in motor function can be variable. This is something that’s actively being studied. We know that in the natural history of the disease, there will be a gradual, slow decline. The pediatric patients will start to reach their milestones, and then they’ll start losing their milestones and gradually get worse. As you get toward the type 2 and 3 patients who present later in childhood, or even those type 3 and 4 patients who present in adulthood, they’ll meet these milestones, but when they start declining, they begin a gradual, slow decline. There are modifiers to that, and that’s what we don’t understand. Why do some people decline faster? Some people decline slower. It may be other genes that are involved. It may be the way they’re managing their disease. There are ways to manage this disease that should be able to slow the decline.

Assessing Motor Function in Later-Onset SMA

: The multidisciplinary team is the future, and this is what has changed in the past 5 to 10 years in the treatment of spinal muscular atrophy [SMA]. Before, it was very much focused on supportive care, or what we can do to help you. With our knowledge and the newer therapeutics that are attacking the disease, this multidisciplinary or interdisciplinary team becomes a very key resource in that. What that will involve is using a combination of physical therapists, occupational therapists, respiratory therapists, speech and language pathologists, and a lot of specialists who are trained in their own particular area and focus specifically on spinal muscular atrophy. What they can do in that multidisciplinary team is provide an exercise program specific to your disease.

We know we don’t want to overexercise people. We know we don’t want to underexercise, because if you don’t do enough exercise, your muscles and joints get stiff. If you do too much exercise on a muscle that’s injured, you can make it worse. We have to find that little window that allows us to do just enough exercise to keep the joints loose and provide some exercise for that muscle but not too much. That’s why the multidisciplinary team includes these specialists—physical therapists, occupational therapists, respiratory therapists, and speech and language pathologists. They’re looking at where you are in your disease and developing a personalized program that’s going to help you to address it. 

I mentioned the exercise. I kept focusing on that, but they’re also going to work on supportive technology. If a patient experiences weakness, is there special bracing? Are there other things that can help? If they’re swallowing, are there tricks they can do to improve the swallowing? What can they do to monitor it? Can they catch a problem before the problem occurs? That’s what the respiratory therapist is going to monitor. They’re working with you as partners in your care based on where you are in your disease, what we can do to identify the next problem before it becomes a problem, and how we can intervene on that.

Tim Hagenacker, MD: Pulmonary care is very important in those patients who have an early impairment of ventilation, or also have problems with coughing and similar symptoms. In those patients, you need an experienced pulmonologist at your center who can take over the care for mechanical ventilation, noninvasive ventilation at night, and prescribing cough-assist devices. This is essential, because it is the most important way to protect patients from severe respiratory infections or pneumonia. 

The gastrointestinal management is also important for the severely impaired patients. The SMA type 1 and 2 patients can have bulbar involvement, so they may have problems with chewing, choking, or other symptoms like that. In these patients, you need good gastrointestinal management to prevent further loss of weight. For that, you need a good nutritionist and gastrointestinal expert, as well.

: The major gastrointestinal complication that can happen in someone with spinal muscular atrophy involves the ability to swallow food and get it into the stomach. This involves 2 parts. We talk about what we refer to as the efficiency and the safety of the swallowing.

The efficiency of the swallow is the ability to put food in your mouth, chew it, and get it into the back of the throat. The safety is the ability to then take it from the back of the throat and get it down into the stomach without it going into the lung. When you see a speech and language pathologist, they’re going evaluate both of those. In the case of spinal muscular atrophy, 1 of the things that can happen that is different from a lot of other diseases is that because of the muscular involvement of the jaw muscles, you get weakness and fatigue in the jaw muscles, which makes chewing very hard.

Patients are not able to chew and get it into the back of the throat. They have problems with efficiency in getting food to the back of the throat. Then they can also have problems with safety. That is, do they send it down the wrong pipe? When they swallow, is it efficient? Swallowing involves multiple muscles. If they don’t communicate correctly, it can go down the wrong pipe and aspiration can happen. We want it go straight to the stomach.

The speech and language pathologist will specifically work with them on exercises. What are the problems or tricks they can do to improve this, and how can they prevent the risk of aspiration?

The best way to manage these potential complications is to get involved with a specialist that can identify where the problems are. Identify if exercises can help. If the disease becomes severe enough that you have difficulty swallowing and you really can’t do it, sometimes you have to think about the use of a feeding tube. A feeding tube is just a way of bypassing the whole swallow. By inserting a tube that goes through the skin directly into the stomach, it allows you to get nutrients straight to the stomach. It doesn’t mean you can’t eat. You can still eat. You can use your mouth just like you would for ice cream or anything. But if there’s a situation where you’re worried about aspiration, you don’t have to worry about that, because you can get all the nutrients you need directly into the stomach.

The complications that we’re going to look for would be whether we need different ways to provide the swallow if it gets bad enough. In milder cases, are there tricks? Are there ways that we can delay the need for a feeding tube? Working with a speech and language pathologist is going to help you try to prevent that.

Diet is another important part that we didn’t even talk about. There are a lot of data out there about which diets are helpful. You want a diet that’s going to be appropriate, and that’s where the nutritionist can help. There aren’t specific SMA diets. There’s no diet that’s been proven to be particularly beneficial. Working with a nutritionist to make sure you get enough calories and are eating the right foods can make a huge difference.

Multidisciplinary Management of SMA

: Nusinersen came out in December 2016. That was a huge event for SMA [spinal muscular atrophy] patients because it was the first medication that would actually treat the underlying disease cause. When we talk about the disease, we talk about SMN1 and SMN2. One percent of SMN2 is abnormal, compared with the normal SMN1. Nusinersen can change the way the protein is produced in SMN2, so it becomes more like SMN1. It doesn’t replace SMN1, but it helps make it function more like SMN1. When you can increase that amount of functional SMN1, you provide the body with the tools it needs to fight this disease.

The introduction of a medication in 2016 that allowed us to directly go in and correct the genetic abnormality was huge. We’ve never had an opportunity like that in neurology. In the clinical trials that got it FDA approved, kids who typically wouldn’t have been able to walk had dramatic improvement with this introduction. It’s been approved across all stages of SMA and in all ages because of its benefit.

Nusinersen has been FDA approved across all stages of SMA, in types 1, 2, 3, and 4. We know from the data that the earlier you get it in the disease course, the more the benefit, but that is still being analyzed. That is still being looked at. 

It is given through an intrathecal injection. That is a spinal fluid injection, so you need a lumbar puncture to do it. There’s a set program that they have in place for how frequently it has to be done. For the most part, it is very well tolerated, except for the obvious complications that can happen from doing any sort of spinal tap. The other potential risks are glomerulonephritis and thrombocytopenia. Prior to any injections, you have to check the liver and blood counts, as well as the renal function to look for any proteinuria. 

Tim Hagenacker, MD: The approval of nusinersen includes all types of 5q SMA, independent of disease severity and patient’s age. When you have a confirmed 5q SMA, you can start treatment with nusinersen.

The mechanism of action is that nusinersen is an antisense oligonucleotide. It involves single-strand genetic information binding to the RNA [ribonucleic acid]. Therefore, it includes exon 7 within the transcript. This is the problem you have with the SMN2 copy number, which codes for a truncated protein with a defect, in contrast to the SMN1 gene. With nusinersen, you make an intact SMN gene out of the defective SMN2 gene. This is the mode of action of nusinersen, and it has to be administered via intrathecal injection, or a lumbar puncture, because it cannot cross the blood-brain barrier. It has to be administered 6 times within the first year of treatment. Four injections are within the first 2 months during a loading phase. Then you have a maintenance phase with repeated injections every 4 months. Independent of SMA type and age, each injection includes 12 mg of nusinersen. 

Nusinersen Treatment for SMA

: The ENDEAR trial is a milestone publication and treatment in SMA [spinal muscular atrophy] because within that publication, SMA type 1 patients were treated with a primary outcome parameter of death or permanent mechanical ventilation. We see that important contrast between the number of patients who reached the primary end point who were treated with nusinersen versus patients who received placebo. This was a really important trial.

Nusinersen was typically well tolerated. There were no severe adverse events. After the approval, some cases of hydrocephalus occurred, which treaters have to be aware of, especially during infancy and childhood. Typically, it is a well-tolerated and efficacious treatment option.

: There were several trials that were done to look at the effectiveness of nusinersen. The CHERISH trial was a phase 3 trial that involved some later-onset disease patients. Those were patients between 2 and 12 years old. From 2 to 12 years of age, they were randomized 2 to 1 to placebo and/or monitored through the disease, looking at the Hammersmith Functional Motor Scale as primary end points. The Hammersmith looks at activities of daily living. Again, that assess activities like rolling over or sitting up. As patients got more involved, because the Hammersmith is involved primarily with proximal function, they had the right Revised Upper Limb Module that was also looked at.

The Limb Module is asking that same question. It’s a functional scale. Can you pick up a coin? Can you raise something up? That’s focused more on the arm, though. They used several functional end points to measure improvement, and they did find statistically significant changes in both of those. The changes were significant enough that when they reached this prespecified interim analysis, the data were so good that the study had to be discontinued. When they completed the analysis and looked at it, and did the final analysis of that interim, the FDA agreed that the study should be discontinued because drug needed to be FDA approved. Between the ENDEAR and CHERISH trials, there were 2 studies showing strong evidence of efficacy, and nusinersen was approved in December 2016.

Well the Hammersmith Functional Motor Scale Expanded, or HFMSE, and the right Upper Limb Module are both functional scales looking at what one can do in terms of activities of daily living, as well as functional use of the arms. Three points are considered to be significant for both of those. When these scales are developed, they ask a series of questions. With those questions, in the case of the right Upper Limb Module, there are 19 questions they ask, and you score them either 0, 1, or 2. One of them is scored on a 0-to-1 scale. You ask those questions and get a score from 0 to 37: 37 is normal, while 0 is at the lower end of the scale

Anytime you see about a 3-point improvement, that’s a significant improvement in quality of life as reported by a patient. Nusinersen showed benefits in both those scales in all the analysis that was done.

The ENDEAR and CHERISH Trials in SMA

: Earlier this year, a group out of Germany published a long-term observational study of about 14 months of patients aged 16 to 55 years old. There were about 139 patients who were enrolled, and they actually analyzed 124 of those. They looked at these patients over the course of 6, 12, and 14 months, as they were treating. This was observational. The patients received their medication through their insurance, the standard way. This was an analysis just looking to see if there was improvement with the nusinersen.

Again, were people were between the ages of 16 and 55 years. They saw at 6 months, using the Hammersmith Functional Motor Scale, that there was about a 28% improvement. At 10 months, 35% of the patients showed clinically meaningful improvement. At 14 months, it was about 40%.

It’s important to remember that those numbers show improvement. As you go further in the clinical trial, the number of people that continue in the clinical trial gets smaller. You get some tricks, in terms of the statistics. But the bottom line on this is that spinal muscular atrophy [SMA] is gradually progressive. 

We know this from the natural history. As we get older, functioning is going to gradually decline more, and now we’ve got a treatment on which, in this observational study, a high percentage of patients either stabilized or showed some modest improvement. That is a huge benefit. It may not have cured their disease, but it prevented the decline. That’s the take-home message from that study.

The trial used the FDA-approved dosing. They had the standard loading dose and then went to the standard maintenance dosing afterward. What I didn’t comment on is that they looked at several parameters. The Hammersmith Scale was the primary parameter. The 6-minute-walk test for those who were ambulatory was 1 of the secondary end points, as was the right Upper Limb Module I mentioned before. They also looked at cost. All those end points showed some partial improvement. This was all using standard, real-world dosing that would be through FDA approval.

The most important part and the key factor in this is that spinal muscular atrophy is known to have a gradually progressive course. This validated what we have been seeing clinically. When we treat patients with nusinersen, we get the reports from the patients that they’re stabilizing. But we don’t have the data that back that up. There have been a couple of scattered reports of single sites based on what they have been seeing. Most of them have been reporting stabilization with this, but they’ll do it on 10, 20, or maybe 30 patients. 

When you start getting over 100 or more, the data become valid. When it’s a small sample, there could be errors or site problems. You have problems with small sample sizes. By going to the larger numbers, you get rid of a lot of those errors. The strength in this is the sample size, for 1. No. 2, there wasn’t a decline. There was stabilization in treatment of SMA.

: In the pivotal trials, only infants and children were treated with nusinersen, but the approval also includes adult patients. Before we had performed that real-world evidence trial within the adult patients, there was a lack of data. That was the reason nusinersen wasn’t reimbursed in every country worldwide. We decided to perform a trial to test the drug within the adult population, and we found that it is also efficacious and safe, as we found in the CHERISH and the ENDEAR trials. For a primary outcome parameter, we chose the same as in the CHERISH trial: the Hammersmith Scale. In the secondary outcome parameters, we chose the Revised Upper Limb Module. For the patients who are ambulatory, the 6-minute-walk test was administered.

In every case, we found a significant improvement of motor function. Especially in the SMA type 3 patients, we also found that with increasing treatment time, an increasing number of patients reached a clinically meaningful improvement of motor function. This does not exclude the SMA type 2 patients. They didn’t have the same amount of motor function increase, but they stabilized. This is also an important treatment goal in the very severely affected patients.

This study is important because it completes the data we also have on infants and children. The important message is that patients cannot be too old to get on treatment, because we don’t find a correlation with patient age. Some of our best improvers in the study were patients who were above 50 years old. It is important that treatment is initiated as early as possible to get the best effects on motor function. On the other hand, patients cannot be too old to get on treatment.

Nusinersen in Adults With 5q SMA

: To my knowledge, there are now more than 10,000 patients on treatment with nusinersen. Within the adult population, more than 3,200 patients are on treatment.



: The nice thing about the German study was that it was in complete agreement with what most of us have been seeing clinically. That is, we treat the patient and we find stabilization of their disease. There may be modest improvements. I don’t see dramatic improvement. But what I don’t see is patients continuing to decline. That’s been the clinical experience of most people that have gone through this treatment.

My own personal experience is biased by the patients that I see, but it’s been well-tolerated and patients have done well.



: In the real world, we have the challenge of some other aspects, which don’t occur in the infant and child population. We also have to deal with very severe scoliosis and similar issues. That contrasts with the infant population, for example, because in the patient with severe scoliosis, you need CT [computed tomography]–guided injection procedure. We have to deal with radiation procedures, radiation exposure, and other aspects of daily problems within the very severely affected patients. Typically, nusinersen is a well-tolerated treatment option, and we were able to perform the treatment in almost every case. There was only a minority of patients who could not be treated by the CT-guided lumbar puncture.

My experience with nusinersen in the treatment of adult patients is that it is typically well tolerated. It’s an efficacious drug. You need good infrastructure at your neuromuscular center. Especially in the very severely affected patients, you need competence in neuroradiology, for example, and in the pulmonology department at your center to get patients on treatment. Patients improve or even stabilize, and we haven’t ever seen this before, so it is an important drug in the treatment of adult SMA [spinal muscular atrophy].

Real-World Experience Treating SMA With Nusinersen

: Risdiplam is an oral molecule that is trying to also increase the amount of SMN2, similarly to what nusinersen is trying to do. It’s a strong advantage that it is an oral medication as opposed to an intrathecal injection. It is still going through some clinical trials and is not FDA approved. We need more data to be certain about its effectiveness, but the initial studies that have come out look very promising. This may be an alternative medication that may work better for some patients with SMA [spinal muscular atrophy]. Being administered orally is a huge advantage.

The mechanism of action is to increase the SMN2 protein. It tries to increase functional protein and transcription of the gene. I’m not sure the exact mechanism is well characterized. It has a similar mechanism to others. That is, to increase the SMN2 so that we can compensate for the loss of the SMN1.

The SUNFISH trial is a later-onset SMA trial. The subjects who were enrolled were between the ages of 2 and 25 years. They were looking for types 2 and 3, not the type 1 disease. Again, they were looking at motor functional scales. They use something called the Motor Functional Measure, on which a 3-point difference was felt to be clinically meaningful.

They had parts 1 and 2. Part 1 has since been released. That showed a clinically meaningful response that was statistically significant in patients who were on the medication. Part 2 is currently under way as a confirmatory study. 

: The JEWELFISH study was mainly focused on safety aspects. It included patients who had prior treatment with another SMN2-dependent drug, like nusinersen. Patients were then switched over to risdiplam. There were no new safety signals. We think that risdiplam has a good safety profile. There were no drug-related adverse events that led to withdrawal of the study drug. We don’t think prior treatment with nusinersen interferes with switching patients over to risdiplam.

: The data so far are saying that the medication has real potential. It needs to go through complete review. It needs to get all the FDA approvals for us to feel comfortable prescribing it. But we have a lot of evidence coming through with this. As clinicians who treat SMA, this presents another potential medication that will hopefully be coming onto the market so that we’ll have multiple ways to treat this disease.

Because of medications like this, SMA has become something where we can personalize the medication. We can decide which of these is going to be the best, and then in combination with the right multidisciplinary care, develop the right exercises. We end up developing an individualized care program that’s specific to each person with SMA.

: Risdiplam is another important drug we need for the treatment of adult SMA because we have patients that get even worse. Also, they were treated with nusinersen, and we have to deal, as I already mentioned, with radiation exposure. We have patients on long-term nusinersen and with every injection, they have increasing radiation exposure. For these patients, and also patients who have severe problems with a neuromyopathic scoliosis and cannot get on treatment, risdiplam is a good option.

Risdiplam Under Study to Treat SMA

: There are still some unmet needs in treatment of the adult SMA [spinal muscular atrophy] population. The important point is that we still need the multidisciplinary treatment approach. The medication does not replace the multidisciplinary approach. It will still be essential. We have these patients who are very severely affected. They don’t have a good number of motor neurons and cannot be improved by a medical treatment focusing on the SMN protein. Stabilization of the muscle itself or improving the muscle function can be a good additional treatment option, in addition to SMN-focused drugs. There are ongoing studies on muscle enhancers and similar treatments. We need these combinations of drugs to get patients within their best motor function. 

: There are several other drugs they are working their way through to try to develop. This is where the excitement happens. We have 2 drugs that we just talked about that are looking to correct the problem. We have an AAV vector that’s already approved for type 1 SMA. If you look down the pipeline, you see a combination of several. There are refinements to the medications that we have now, but we also have a whole other group of medications that are working their way through that to try to enhance the muscle function. 

These work across different neuromuscular diseases. Remember, earlier we said that the medications can arrest the process. We didn’t know if it was going to improve things, but the goal was simply to arrest the process. Now we want to get the muscles functioning better. We want to improve their function. There are medications in clinical trials that they have to sort out. If they work, they have to sort out their efficacy. There’s a long way to go before they can come out. But if they do show the benefit that we’re hoping we will see, then we’ll have something that we can put on top of the SMN2 medications to try to get the muscles to function better and stronger, and for people to do better.

Drugs in Development and Next Steps

: The treatment of spinal muscular atrophy has really changed over the past 5 years. If you’re treating patients with spinal muscular atrophy [SMA], getting to know your physical therapist, occupational therapist, speech and language pathologist, and all your treatment partners is critical. Working together with them to come up with a very comprehensive plan is going to be the best way to address this. There’s so much more we can do these days that we haven’t been able to do in previous years. We have the medications, we have future medications that may come onto the market, and we have a much better understanding of the role that exercise and these multidisciplinary clinics will play. Getting that together, whether it’s referring to 1 of these clinics or doing it by yourself with the specialist to get the training, is important. It’s all available to understand what we need to do. It’s amazing where the disease is going to go in terms of treatment because of those.

: The most important information is that SMA is now a treatable disease. Every neurologist has to keep that in mind, because many of us are treating these patients for a very long time, and patients come more for that multidisciplinary team approach. The neurologist was more the administrator who collected the information, but now, we are switching over to an active role. This is important that we are now more on the active side. This is an active part of our profession. We have to offer these treatment options to the patient and give good advice on which will be the best treatment option for every individual SMA patient.

Updates in Treatment of Adult Spinal Muscular Atrophy