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Challenges in Clinical Decision-Making for Patients with Spinal Muscular Atrophy

Challenges in Clinical Decision-Making for Patients with Spinal Muscular Atrophy 1024 683 Mary Bates, PhD

There are three approved genetic therapies for SMA, but little guidance in treatment selection.

Spinal muscular atrophy (SMA) was once a leading cause of inherited infant death in the United States. Today, there are three genetic therapies approved by the Food and Drug Administration to treat SMA — but no clinical trials directly comparing treatment options. In a new paper, Megan Waldrop, MD, a pediatric neurologist at Nationwide Children’s Hospital, highlights how this poses challenges for clinical decision-making.

“It’s exciting now that we have three ways to treat SMA that all lead to significant changes in outcomes,” says Dr. Waldrop. “These are very good therapies, but we still have a lot to learn about how to best care for patients with SMA.”

SMA is an inherited neurodegenerative disorder resulting from the loss of spinal motor neurons. Patients with the most severe form of SMA, type 0, have symptom onset in utero, while those with the mildest form, type 4, do not experience symptoms until adulthood.

Since 2016, three genetic therapies have been approved for the treatment of SMA: Nusinersen, an antisense oligonucleotide that is delivered by lumbar puncture; onasemnogene apoparvac or Zolgensma, a gene replacement therapy that was developed at Nationwide Children’s; and risdiplam, a small molecule that is taken orally. All three therapies increase the amount of survival motor neuron protein that individuals can make and result in improvements in motor milestones and functional outcomes. The therapies differ in mechanism of action, administration and potential side effects and complications.

Currently, treatment selection for SMA is variable and largely determined by clinician preference and insurance coverage. Clinical decision-making is complicated by the fact that there are no head-to-head comparator studies of all three treatments. In addition, the clinical trials for each treatment involved different populations of SMA patients, including infants identified via newborn screening, symptomatic infants and children and symptomatic adults.

“At Nationwide Children’s, we talk with the families about the risks and the benefits of each therapy,” says Dr. Waldrop, who is also an assistant professor of pediatrics and neurology at The Ohio State University College of Medicine. “We review the data and study population for each treatment. Then, taking into account the blood work and our assessment, we help guide them in their choice of treatment.”

Dr. Waldrop says that during her career, she has seen the treatment options for SMA evolve. “I remember when we didn’t have treatments for patients with SMA,” she says. “Now, we have three, and I think those are going to continue to evolve. We will learn about this new natural history of SMA as these individuals live well into adulthood. It’s an exciting time.”

 

Reference:

Waldrop MA. Clinical decision making around commercial use of gene and genetic therapies for spinal muscular atrophy. Neurotherapeutics. 2024 Jul;21(4):e00437. doi: 10.1016/j.neurot.2024.e00437. Epub 2024 Sep 5.

About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.

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