The Overlooked Burden of Bulbar Symptoms in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder caused by biallelic variants in the survival motor neuron 1 (SMN1) gene, leading to degeneration of motor neurons in the spinal cord and progressive proximal muscle weakness.¹ The approval of 3 SMN-enhancing therapies, including nusinersen (Spinraza; Biogen), onasemnogene abeparvovec (Zolgensma; Novartis), and risdiplam (Evrysdi; Roche), together with the adoption of newborn screening in all 50 states,² has changed the natural history of the disease so substantially that presymptomatic treatment is now the expectation rather than the exception.

That success has produced its own difficulty. Patients treated before symptom onset are reaching childhood and adolescence with function that the historical type classifications do not describe, and the questions that remain are less about whether motor neurons can be rescued than about which ones are not fully rescued. Among these, the nerves governing speech and swallowing have drawn comparatively little systematic attention, even as patient surveys identify bulbar symptoms as a substantial burden in adulthood.

Dustin Gable, MD, PhD, is an assistant professor of neurology at Johns Hopkins University School of Medicine and a pediatric neuromuscular attending in the Division of Pediatric Neurology. He completed his MD and PhD in human genetics at Johns Hopkins, a combined residency in pediatrics and neurology at Boston Children’s Hospital, where he also pursued postdoctoral work on lower cranial motor neuron development, and a neuromuscular medicine fellowship at The Johns Hopkins Hospital. His laboratory research, supported by the Child Neurologist Career Development Program-K12, focuses on SMA and bulbar dysfunction.

In recognition of SMA Awareness Month, held annually throughout August, NeurologyLive^® spoke with Gable about how the arrival of genetic medicine reshaped the field midway through his training, how he views the neurologist’s position in the broader care team, and why he considers newborn screening the single most consequential change of the treatment era. He also discussed the misconception he encounters most often, and why he has directed his research career toward the nerves that control speech and swallowing.

NeurologyLive: From your clinical perspective, how has your understanding of SMA’s impact on patients and their families evolved over your career?

Dustin Gable, MD, PhD: When I was doing my PhD in human genetics, and when I started, we had many discussions around 2011 and 2012 about gene therapy and gene-directed therapies, and whether and when that would be possible and whether it would be effective. As I finished my PhD and went back to medical school, that’s around the time that nusinersen was coming to light and being shown to be incredibly effective.

In a few quick years, there was this boom of genetic medicine and amazing responses and treatment effects from the patients that I got to see as a medical student. It completely changed the field and the paradigm both of neurology, pediatric neurology, and genetic medicine. I remember watching some of the initial videos of the patients who received the therapies and watching them walk, and it was really profound. I am so excited to continue in this area since then.

Not only have those therapies evolved to allow for multiple different types of therapies, depending on the patient’s preference, but we also have new modes of therapy targeting muscle on the horizon, and we have new therapies that are more accessible for some of the older patients with SMA. I will end by saying that one of the most exciting advancements, in large thanks to Cure SMA, is the implementation of newborn screening in every state in the United States, which allows for early detection and initiation of presymptomatic therapy, and that has changed outcomes in dramatic ways.

What does the typical care journey look like for a patient with SMA, and where does your role fit into the broader care team?

I think this conversation is one of the most important ones, because patients with SMA live in every part of the world, and depending on where we are, we have different resources at hand. The center of care for these patients really is our primary care physicians, who help guide them to neurologists. And then the neurologist, or the pediatric neurologist, is where we sit as the central hub, to help confirm the diagnosis, monitor disease progression, and help the families make decisions with gene therapy and disease-modifying therapies. These are time-sensitive decisions. They require specific SMA expertise, and it is very important that the families feel supported.

Beyond the neurology teams and the primary care physicians who help so much in guiding the care across systems, the teams that are really important to stay in contact with, and that just do incredible work with the patients, are the rehabilitation physicians, the physical therapists, the occupational therapists, and the speech therapists. They change these patients’ lives in profound ways, and it’s becoming more and more common that these therapists and rehabilitation specialists are centralized in places that the patients can come to and get both their disease-modifying care and their rehabilitation care.

I will add that it is very important that patients follow up with pulmonology, our gastroenterology colleagues, and our orthopedic colleagues. We need support for nutrition. We need support for understanding where they are in their lung function and where we can support them, and that requires pulmonary function testing and regular monitoring. The gastroenterology and nutrition component requires regular weight check-ins and checking different vitamin and nutrient levels. Then with orthopedics, working with scoliosis and contractures.

Our genetic counseling team is another discipline that really helps when the families are getting the diagnosis and also with family planning, and it is always important to consider working with our psychology teams if and when needed. Together, between neurologists, primary care physicians, rehabilitation physicians, pulmonologists, gastroenterologists, orthopedics, and genetic counseling, this is the multidisciplinary clinical world for these patients in the current state of the United States.

What has been the most meaningful shift you have seen in SMA treatment or management since the approval of disease-modifying therapies?

The fact that newborn screening is available in all 50 states has changed the game. It allows early presymptomatic treatment, and we know after numerous outcome studies that it’s clear as day that early presymptomatic treatment leads to better outcomes. We still have problems, and we have things that we are working on with patients after presymptomatic therapy, but we know their outcomes are much better, and the likelihood of having better outcomes is high.

What is one misconception about SMA care you would like clinicians to understand better?

One of the things that I hear commonly is that we have “cured” SMA. We have made amazing gains, and we have in so many ways made pivotal movement in these patients’ lives. With the current therapies, we have patients living longer and healthier lives, and often free of symptoms.

But we still have the horizon to look at when our patients are 20 years, 30 years, and 40 years old. We have our adult populations who currently have SMA and were not able to have access to therapies early. We also have different parts of the world where patients have a burden of disease that needs our support and our attention. So, the prevalence of SMA will in some ways increase, and that means the work is not finished.

Looking ahead, what unmet need or open question in SMA care are you most focused on right now?

For me, it’s bulbar function, the ability to speak, the ability to swallow, to articulate our words and to be heard, and to be able to eat comfortably at dinner. This is a burden of disease that has not been systematically characterized until recently, and treatments and diagnostics have not been standardized, especially in the new era of the new therapies, to really assess the burden of disease in patients.

The nerves that control those functions are very vulnerable, and we see in outcome studies and in patient surveys, especially with patients in adulthood, that these are a huge burden of disease. We really at this point need more basic science research, we need more clinical documentation, and we need more systematic approaches to assessing bulbar dysfunction in SMA. That requires insight from every provider who cares for them. We have some great leaders in SMA who are starting to lead the way and spearhead retrospective and prospective assessments of the burden of disease, to help us understand what diagnostics are necessary and what therapeutics are necessary.

These symptoms and the nerves that control these functions need more attention and more research to understand how the current therapies can be optimized, and also whether there are additional therapies that these nerves might respond better to, which requires basic science and mechanistic science. My work in the lab is focused on understanding why those nerves are particularly vulnerable, in addition to the nerves that control our arms and legs. By treating bulbar dysfunction and thinking of it systematically, like we have with the spinal motor neurons in the arms and the legs, I think that we can make significant headway for the patients.

Is there anything else you would want to add about why raising awareness of SMA matters?

If I had to say anything to add, it is how inspiring it is to work with these patients, to see the families work with the patients, and to go through this process with so much strength and courage and dedication to the cause. It has been motivating for me to be a new pediatric neuromuscular provider, and it has given me direction in my own career.

I think what we do with research in SMA will serve as a paradigm for other genetic diseases. What we learn and how we improve SMA will stretch to many different diseases, especially motor neuron diseases, I hope, in the future. So I think that this is a field that is exciting to be in, that needs a lot of work, and that has wonderful researchers, physicians, and community teams here to support the patients.

I also want to acknowledge the mentors who inspired me to be in this field, including Elizabeth Engle, MD, Basil T. Darras, MD, Leslie H. Hayes, MD, and Partha S. Ghosh, MD, at Boston Children’s Hospital, and here at Johns Hopkins, Charlotte J. Sumner, MD, in whose laboratory I work, and Jessie Nance, MD, Matthew J. Elrick, MD, PhD, and Thomas O. Crawford, MD, in clinic. They have really moved the needle and are bringing new researchers into the field, and also inspiring younger ones.

Transcript edited for clarity. For more perspectives on the multidisciplinary care approach in SMA, click here to read our previous Q&A in this series.

REFERENCES
1. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015;51(2):157-167. doi:10.1002/mus.24497
2. 100% of States Now Screening Newborns for SMA. News release. Cure SMA. January 3, 2024. Accessed August 24, 2026. https://www.curesma.org/100-of-states-now-screening-newborns-for-sma/