HCP Live
Contagion LiveCGT LiveNeurology LiveHCP LiveOncology LiveContemporary PediatricsContemporary OBGYNEndocrinology NetworkPractical CardiologyRheumatology Netowrk

Spinal Muscular Atrophy (SMA): Physician and Patient Management - Episode 9

Life During Therapy: Good Days and Bad Days

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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?

Sebastian Mills: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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?

Sebastian Mills: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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.”

Crystal Proud, MD: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: You don't find any evidence that patients, with time, are becoming tolerant to the infusion?

Crystal Proud, MD: No.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: The success rate really is phenomenally high, isn't it?

Crystal Proud, MD: Incredibly high.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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?

Crystal Proud, MD: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: Which is relatively newer isn't it?

Crystal Proud, MD: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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?

Crystal Proud, MD: 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.

Philippa Cheetham, MBChB, MRCS, MD, FRCS: 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?

Crystal Proud, MD: Absolutely, yes.