Rare Disease Stories of Success: Newfound Hope for Spinal Muscular Atrophy

Mary Schroth, MD, FAAP, FCCP

Rare Disease Day, observed annually on the last day of February, aims to raise awareness about rare diseases, which affect over 300 million people worldwide, and to advocate for improved access to diagnosis, treatment, and care. The global event gathers patients, caregivers, healthcare professionals, and policymakers to spotlight the challenges faced by those living with rare conditions and to foster greater research and support initiatives.

Spinal muscular atrophy (SMA), a rare, genetic, and progressive neuromuscular disorder, is found in approximately 1 in 10,000 live births, affecting both children and adults, though the severity can vary. Globally, the prevalence of SMA is thought to be around 1 in 50,000 people; however, this can range slightly depending on the population being studied. SMA also occurs in different forms, with the most severe being Type 1, which usually appears in infants, and milder forms such as Type 3 and Type 4 that can manifest later in life.

As part of NeurologyLive’s efforts to raise awareness for Rare Disease Day, Mary Schroth, MD, FAAP, FCCP, chief medical officer at Cure SMA, sat down for a conversation about the remarkable progress made in SMA. She spoke on the landmark approvals of 3 medications and the nationwide implementation of newborn screening, which has transformed outcomes for affected infants. Schroth also emphasized the importance of continued awareness efforts, especially around SMA treatments and limitations in newborn screening, as well as advocated for supporting the growing population of adults living with the condition. Furthermore, she discussed the critical need for ongoing basic research to identify new therapeutic targets and work toward a future cure.

How far has the SMA community come in recent decades?

Mary Schroth, MD, FAAP, FCCP: Right now, we're in an amazing place for spinal muscular atrophy (SMA). SMA is a neurodegenerative and progressive genetic disorder. We can celebrate that we have three FDA-approved treatments that target the genetic cause of SMA. SMA is caused by low levels of the survival motor neuron (SMN) protein, and these drugs, through different mechanisms, increase the level of SMN protein in the body.

We can also celebrate that newborn screening for SMA is available for all infants born across the U.S. Together, early diagnosis and early treatment provide the best outcomes for SMA. We are seeing children with two copies of the SMN2 gene—who, prior to treatments, were expected to have the most severe form of SMA—now walking before the age of two years. It’s been truly amazing to see.

What efforts have been made to improve newborn screening practices?

We’ve collaborated with healthcare professionals to publish updated SMA best practice recommendations for diagnosis considerations. These were published in Neurology: Clinical Practice in 2024. The updated recommendations emphasize the importance of SMA newborn screening for achieving the best outcomes. They also provide detailed information about implementation and the roles of the diagnostic laboratory, the primary care provider, and the SMA specialty care team.

One limitation to be aware of, though, is that although 95–98% of infants with SMA will be identified, 2–5% are not detected with the current genetic screening and may develop symptoms before diagnosis. Therefore, both parents and clinicians must be aware that when an infant presents with weakness, SMA should still be considered as a possible cause—even with a normal SMA newborn screen. Additionally, our publication outlines symptoms in adults that should trigger consideration of SMA.

Are there aspects of the disease that are lesser known by the public?

There’s clearly growing awareness about SMA, and at Cure SMA, our focus is on sharing information and providing education to increase that awareness—both about SMA and the treatments available.

That said, there are still areas where healthcare providers are not fully aware that treatments for SMA exist. The reality is that most people become aware of SMA when someone in their family or among their friends and acquaintances is affected. What the public may not realize is that, although we have treatments for SMA, we do not yet have a cure. The current treatment options are life-changing, but they are not curative. We are not done developing new treatments or working toward finding a cure.

How can we continue to support adults living with SMA now that survival has been extended?

Currently, over half of people living with SMA in the US are adults. Cure SMA actively engages adults with SMA to learn more about their unmet needs and priorities.

It’s really important to hear directly from our adult community about what they need. We reach out through our Adult Advisory Committee, the annual SMA conference, and an annual survey to our members about their experiences living with SMA. We then leverage this information to guide our advocacy efforts, community support programs, and research and care initiatives.

From a funding and research perspective, where do efforts need to be directed going forward?

It’s essential that we continue to fund basic research. Basic research improves our understanding of SMA’s disease mechanisms, and many things we’ve learned from SMA have been translatable to other neurologic disorders.

This research helps identify potential targets for drug development as well as a future cure. In the past 2 decades, Cure SMA has funded over 139 basic research grants. These projects have advanced our understanding of SMA and provided early funding for research that ultimately led to the development of our currently approved, genetically targeted therapies.

While the approved therapies have dramatically altered the disease, they are not cures, and there remain significant unmet needs—especially for older and symptomatic individuals. Right now, we anticipate several new investigational drugs to be submitted for FDA approval in the coming months.

Some of these new drugs focus on non-SMN targets, like muscle, and may be used alongside current SMN-directed therapies. Cure SMA is committed to continuing basic research to better understand what happens in the body when SMN protein levels are reduced in SMA and to identify new druggable targets to combat those effects.