Perry Shieh, MD, PhD, Professor of Neurology and Pediatrics at the University of California Los Angeles (UCLA) with expertise in neuromuscular diseases, talks about the first and only at-home treatment for SMA in adults and children two months of age and older.
Can you tell me what is SMA and how it impacts kids?
SHIEH: SMA is spinal muscular atrophy. That’s a term we use for genetic causes of this progressive degeneration of the nerves that control muscles. We call them motor neurons. Another motor neuron disease that some people might be familiar with is ALS. ALS can be genetic or not, whereas spinal muscular atrophy is genetic. It’s what we call a recessive disease which means the parents are generally carriers and don’t have the disease, but they can pass on a gene which is defective to their child. If they each pass on a gene that’s defective to the child, so the child has two defective genes, they can manifest this disease.
What would parents start to notice in a child who has SMA?
SHIEH: It’s a disease with a significant spectrum. We have the most severe patients present when they’re infants, usually within the first couple of months of life. We tend to call this the infantile onset or the severe infantile SMA. The infantile form is type 1, the intermediate form is type 2, and the mildest form is type 3. The type 2 patients are patients who are milder and do attain the ability to sit independently, whereas the most severe infantile patients never are able to sit on their own. They’re never able to hold their head up. Type 3 patients are defined as patients who are able to stand and walk. The most common is the infantile form. Parents usually notice that there’s something wrong, especially if it’s their second or third child, that their child is not achieving things or achieving motor skills they would normally expect their child to do. On the milder end of the spectrum, it’s a little harder to diagnose and a little harder for parents to notice because it’s milder
Is it a disease that is fatal?
SHIEH: The most severe form, the infantile onset, is fatal. Clinical studies have shown 90 percent of patients with infantile onset typically do not live past their second birthday.
Are there treatments for children who are on that spectrum and maybe don’t have the most severe form?
SHIEH: Prior to 2016, we only had supportive treatment. These patients have progressive muscle weakness, or muscle wasting. Their muscles are basically shrinking. This means they aren’t able to move their arms around, and they eventually have difficulty swallowing and breathing. That’s our essential functions to life. We can keep them alive. We can give them a feeding tube. We can do a tracheostomy, which is to place a little hole and connect them to a ventilator to force air into their lungs because their diaphragm and other muscles that help them breathe don’t work so well. In the past, we’ve treated these patients to keep them alive according to the parents’ wishes. After 2016, however, we started to see treatments available and now there are three medicines available to patients who have spinal muscular atrophy. All three of these treat the underlying cause of the disease being these patients are missing a protein called SMN. It’s relatively deficient and these three medications help the body make that protein which is a very important protein to try to keep the nerves, or motor neurons, alive. By keeping them alive, these patients will have a better outcome. They’re going to, in the long run, be able to preserve their muscle strength.
Can you talk a bit about Evrysdi treatment and who it’s best suited for?
SHIEH: Evrysdi is an exciting development because it’s the first medication that can be taken orally. The other two medications had to be injected. In fact, one of them, the first medication that was approved, required injections into the spine every four months. That’s a very effective treatment, but you can see why a lot of people might be afraid with having injections in the spine. However, people underwent these treatments because it made a difference in their lives. Evrysdi provides the option of being able to take the medication at home. And, if it needs to be given through a feeding tube, it can be given that way because it’s a liquid. So, typically the patients take at most six and two thirds of a millimeter, which is a little bit more than a teaspoon.
How important is it to have some of these new treatments and therapies for this population of patients?
SHIEH: This disease is progressive, so that means when these patients are born, they have the greatest number of neurons that they will ever have and just start to lose them gradually through life. It could happen relatively quickly in the patients who have infantile or type 1, or in the mildest patients it may happen so slowly that they won’t notice until they’re a few years old. All three of these medications help to preserve those nerves from dying or degenerating. As a result, the long-term outcome is very important, and to be able to preserve motor function is to be able to preserve the nerves and prevent them from dying.
Will they get any of that function back with these drugs? Or, once they’ve lost it, it’s not coming back?
SHIEH: We didn’t really expect that patients who were treated with any of these medications would gain back any of the motor function that they had lost. The truth is, it’s not as simple as neurons being alive and dead. There’s sort of this intermediate sick state that they could possibly be in. Patients who have been treated with one of these medications, sometimes gain function. We’re thinking that perhaps it’s because some of these nerves, or neurons, that were in that sort of dormant or sick state, woke up to some extent. And that provided more motor function to some of our patients. That’s been very encouraging. I think it’s very encouraging for the patients to see that they do gain a little bit of motor function sometimes if they start one of these medicines.
I wanted to ask you about the importance of infant screening. Some states have pretty robust screening programs, and it varies state by state. How important is it for parents to have this knowledge early on?
SHIEH: It’s been shown through our studies that early treatment makes a difference because this is a progressive disease. Your best shot at preserving motor neurons is from the day these children are born. We want to diagnose these patients as early as possible so we can start treatment as early as possible. It was recommended to the screening panel that all states screen for these diseases and SMA was added to that list back in 2018. Fortunately, many of the states in the United States have implemented this screening. As of today, somewhere in the order of 68, 69 percent of all infants that are born in the United States will be screened for spinal muscular atrophy as soon as they’re born.
Is there anything I didn’t ask that you want people to know either about SMA or about treatments and treatment options?
SHIEH: This is a devastating disease and it’s devastating for the families that have infants. For our patients, including the ones that are already grown up, and even the ones that are not born yet, this provides incredible hope. It makes a big difference. I can’t say that they’re going to be normal, but the newborns have the best chance at having the most amount of function. Some of them might be normal once they grow up. It depends on how early we catch them and how severe they would have ended up. So, this is really a game changer for our field. We’re talking about different ways of taking care of these patients. Now, in the future, we’re talking about less ventilators, less surgeries, and figuring out how to be able to give them as much independence as they can.
Statistically, do you have any numbers on how many kids are living with SMA in the United States?
SHIEH: I don’t know exactly what the number of SMA patients are, but I would say that it’s one in about ten thousand live births. That number is going to fluctuate and start shifting now because many of them are going to live a lot longer given all the medications that are available now for what we call disease modification. We’re going to see much better longevity and that’s going to increase the prevalence of this disease. Hopefully, many of them will be independent and functional.
Are these treatments covered by insurance?
SHIEH: Insurance is paying for these treatments. It’s very costly to have a patient who has SMA who’s not treated. And, to some extent there are cost offsets. So, although these medications tend to be expensive, it also does make a difference in these patients lives. It makes a difference in the cost of their care as well.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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