Julie Parsons, MD, and John Brandsema, MD, open a discussion surrounding prevalence of spinal muscular atrophy (SMA).
Julie Parsons, MD: Spinal muscular atrophy [SMA] is a neurodegenerative disease that affects principally the motor nerves, or the motor neurons, in people. The motor neurons provide function and strength to muscles, and allow muscles to contract. This genetic disease is a disease of the motor neurons, so patients progressively become weaker and ultimately die because of the inability to breathe or eat. We think the frequency of SMA is 1 in 10,000 to 11,000 patients, so it’s a fairly rare disease. But prior to the advent of the disease-modifying therapies, it was the leading cause of genetic death in children under the age of 2 years.
John Brandsema, MD: We consider this a spectrum disease, in which the most common form is unfortunately the most severe and has infantile onset. Two-thirds of patients present with what in the past was called type 1 SMA, never achieving the ability to sit on their own. With the next most common form, which was called type 2, patients achieve sitting but never walking independently in the natural history. Then there are people with SMA who walk but at some point in their lives may lose that ability because of the progressive loss of function that happens with the disease.
Now that we have targeted treatments for this disease, we’ve changed our classification of the patients over time. The old terms of type 1, 2, and 3, which were the versions that we tended to see in childhood, aren’t as relevant because people can change categories based on development happening on a stabilized nervous system. But they still have use in terms of appreciating the constellation of symptoms that we might see associated with each type. As the disease becomes more severe, we tend to see bulbar involvement, which is the breathing and swallowing issues that can present, in addition to the limb weakness that’s universal in SMA. The bulbar issues tend to lead to life-threatening complications of recurrent respiratory failure and an inability to maintain nutrition unless it’s fully supported.
Because of the spectrum of severity in the natural history, we’d have patients coming to clinic who were very severely affected and needed a lot of interdisciplinary management. Our main colleagues who we work with on SMA care include orthopedists because of joint contracture and progressive scoliosis of the spine seen in the more severe forms. Pulmonary management is also very important because respiratory failure can be an early part of the symptomatology of the severe forms. GI [gastrointestinal] management in terms of motility is also a significant concern. We may involve other specialties as well depending on level of severity.
This is now changing in terms of the ability to target SMA with some of our targeted treatments for the disease, in which we may not see the same progression of symptomatology in patients that we saw in the natural history, and we need to adapt their care model because of that. But the spectrum makes that burden highly variable in this disease in terms of how often they’re accessing care. If we had somebody with infantile onset of the disease with no opportunity for treatment, we’d need to see them quite frequently—sometimes monthly—because of the rapid respiratory and nutrition issues that they’d start to face, to help with all the different aspects of what’s deteriorating. Whereas if somebody with SMA is able to walk, we often can see them twice a year or even annually and meet all their care needs sufficiently.
On treatment, sometimes we’re able to space this out a little from the perspective of the clinical needs. But the flip side is also true: if we’re on targeted treatment, some things need to be monitored or practically done related to those treatments that need interaction with the health care system. It’s a very individualized care plan. On average, a patient with SMA is seen once or twice a year at minimum, but much more frequently if there are changes happening or there’s severe involvement of their bulbar system.
Julie Parsons, MD: We’re also seeing patients interact with the health care system on an individual basis. When patients are more severely affected, we see them much more frequently. We may see older patients or patients who are ambulatory—able to walk—on an annual basis as well. It depends on the ongoing medical issues patients are experiencing.
With disease-modifying therapies, particularly with gene transfer therapy, visits are very frequent during the first several months post-treatment because we’re monitoring laboratory assessments and physical exams very closely. It’s interesting that when we use disease-modifying therapies, we continue to need to follow patients closely, even if they’re doing very well, because we’re still learning about the outcomes and long-term outcomes of patients treated with disease-modifying therapies. I agree with Dr Brandsema that some patients need to be seen almost monthly, and others can be seen on an annual basis. It depends on the individual and their clinical needs, which our team assesses at their appointments.
Transcript edited for clarity.