Challenges and Considerations in Treatment of Adult Spinal Muscular Atrophy - Episode 2
John Brandsema, MD: When discussing the impact of SMA [spinal muscular atrophy] on a patient’s overall quality of life, you have to consider the huge variability in how this disease affects people depending on their genotypes. This means looking at their copy number of SMN2 and how many copies of the backup gene they have making the SMN protein that their body is lacking. When they first presented with symptoms, was it the most severe early onset as an infant? Did they start having symptoms much later in life? We can then start to think of categories of functions.
In the natural history, we used to describe types of SMA defined by the maximal motor function that someone would achieve, such as sitting or walking. Nowadays, because targeted treatments sometimes blur these lines a bit, we’re starting to think of 3 broad categories of SMA function. We have nonsitters: those who are unable to sit independently. We have sitters who can sit but cannot take independent steps by themselves. We also have walkers with SMA.
Those groups are different in terms of the overall experience of their symptoms because those who are more mildly affected don’t tend to have some of the bulbar effects that we see in the more severe forms that can affect things like speaking, swallowing, needing supplemental nutrition, and sometimes alternative feeding through things like the G-tube [gastrostomy tube]. They also don’t tend to have as much breathing involvement with the need for BiPAP [bilevel positive airway pressure] support at nighttime or sometimes even daytime respiratory support, as well as the vulnerability to respiratory infections that can come from chronic respiratory failure. The orthopedic implications of milder SMA are also not present, whereas in the more severe forms, things like scoliosis, limb contracture, hip dislocation, and all these other orthopedic sequelae that we see with this progressive weakness are much more of a consideration for patients.
You could imagine that a 19-year-old living with SMA could be somebody who had infantile onset of their disease with a very rapid loss of strength and is now barely able to move their fingers just a flicker, living entirely on tracheostomy support for their breathing and needing full feeding via a G-tube in terms of their nutrition. It could also be somebody who’s just starting to experience weakness and is having a type 4 onset of their disease but is otherwise entirely normal. They may just have some subtle difficulty with exercise tolerance or a bit of difficulty with stairs.
As you can see, both of those people have SMA, but they are very different in terms of the impact on their quality of life. What I will say in general is that this is a neurodegenerative disease, so regardless of when you have onset of symptoms, what you will notice over time is that your strength is worse and that you’re dealing with more symptoms and more burden. This can be very impactful for the overall quality of life for the patients themselves, such as having limitations to their function, living in fear of catching a respiratory infection and ending up in the hospital with extra need for respiratory support, and having chronic pain and other things related to positioning and orthopedic considerations.
It also has a significant impact on all the caregivers involved in that person’s life: their family members, their loved ones, people with whom they are romantically involved, or people who are nursing or caregiving for them. All these people are touched by the person living with SMA’s symptoms and their friends and some social contacts as well.
It’s a disease that really affects every aspect of somebody’s quality of life, and it’s very clear that quality of life is impacting in this disease. However, when we do objective measures of it, people living with weakness find ways to cope and can have quite a high-quality life in terms of their perceptions of their own health and well-being.
In general, it’s important to keep in mind that things like anxiety and depression are more common when living with a chronic illness, so we need to be vigilant for that in our long-term follow-up with these patients.
Consultant: Alexion, Audentes, AveXis, Biogen, Cytokinetics, Genentech, Momenta, NS Pharma, PTC Therapeutics, Sarepta, Scholar Rock, WaVE
Research support: Alexion, Astellas, AveXis, Biogen, CSL Behring, Cytokinetics, Fibrogen, Genentech, Pfizer, PTC Therapeutics, Sarepta, Summit, WaVE
Speaker: AveXis and Biogen