How Gene Transfer Therapy and New Screenings Transform Spinal Muscular Atrophy Outcomes

A decade ago, a spinal muscular atrophy (SMA) diagnosis often meant that a child would eventually become paralyzed and require a tracheostomy and G-tube. Although there’s still no cure for SMA, recent advances in diagnostics, treatments and newborn screening are ensuring a much brighter future for children with this neurodegenerative disorder.

Diana Castro, M.D., Pediatric Neurologist at Children’s Health℠ and Associate Professor at UT Southwestern, leads one of the nation’s largest pediatric neuromuscular departments and has been a world leader in SMA for a decade. Children’s Health is the only CURE SMA Care Center Network in Texas, which means we’re part of a national network that demands the highest standards of care for SMA.

“We're turning the corner completely for this condition,” Dr. Castro says. “We’re diagnosing and treating patients earlier than ever, and we're seeing drastic improvements in motor function, respiratory and mortality outcomes as well as quality of life outcomes. It’s critical for neurologists, and any providers who care for babies and their families, to be aware of SMA and the need for early screening and treatment.”

The Importance of Newborn Screening for Spinal Muscular Atrophy

SMA affects approximately one in every 11,000 live births, but one in every 50 American adults are genetic carriers. When both parents are genetic carriers, their probability of having a child with SMA is about 25%.

“There are four types of SMA that vary in severity of symptoms, age of onset and rate of progression. SMA Type 1 is the most common and severe with neurodegenerative symptoms beginning in the first few months of life,” Dr. Castro explains. “We’ve learned from recent clinical research that all SMA patients can experience life-changing results, particularly motor and respiratory outcomes, if they receive a targeted treatment within the first six weeks of life.”

The problem is that most babies are presymptomatic in those first six weeks. Newborn screening for SMA is crucial to diagnose and treat babies within this period, but not all states have SMA on the newborn screening panel. Dr. Castro and her team advocated for SMA to be added to the panel in Texas, and it was officially added on June 1, 2021.

Now, a sample is collected within 24 hours of birth and submitted for testing by the Texas Department of Health. The test result is usually available within five days. If the test is positive, the baby’s pediatrician and a neurologist specializing in SMA are notified immediately.

Since SMA was added to the panel, there have already been four newborns diagnosed with SMA at Children’s Health. The newborn screening not only expedites care for these babies because of early detection, but it also ensures that three entities – the Texas Department of Health, pediatrician and neurologist – are in direct communication and working side-by-side to treat the baby as fast as possible.

For example, in August 2021 Dr. Castro was notified of a newborn with a positive SMA test result by the seventh day of life.

“Within 24 hours of the test result, I had spoken to the pediatrician and the family, and began moving forward with a confirmatory test and studies to determine the best treatment,” she says. 

Does Newborn Screening Detect All SMA Patients?

About 95% of SMA patients can be detected by newborn screening. These SMA cases are caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene, which means both copies of the gene are deleted. About 5% of SMA cases are caused by SMN1 gene sequence mutations, and these patients are not detected by newborn screening.

“It’s very important for pediatricians to closely monitor babies who are not meeting developmental milestones, have low muscle tone and low reflex responses, so they can identify those 5% of SMA patients,” Dr. Castro says. “SMA testing is free nationwide, so there is no loss in getting a test for a baby who is showing possible SMA signs, and there’s everything to gain if the baby is positive. Every day counts.”

Three Advanced SMA Treatments

ZOLGENSMA® (onasemnogene abeparvovec-xioi) is a gene transfer therapy that was FDA approved in 2019 to treat SMA. This therapy uses a AAV9 viral vector to deliver the SMN1 gene to the patient, enabling them to produce SMN protein.

The two other key therapies include SPINRAZA® (nusinersen), which was FDA approved in 2016 for all ages, and Evrysdi® (risdiplam), which was FDA approved in 2020 for patients older than two months. Both therapies treat SMA by enhancing the SMN2 gene to increase SMN protein levels.

“There’s been incredible progress in just 10 years of clinical research, and we’ve been involved with all three FDA-approved SMA therapies since Phase 1 clinical trials. That gives us firsthand insight to how these therapies can have life-changing impact,” Dr. Castro says. “The next groundbreaking research for SMA investigates drugs that target other aspects of the disease, such as Myostatin Inhibitor to enhance muscle fiber growth.”

Two Sisters with SMA, Two Very Different Outcomes

The rapid SMA progress is illustrated by two sisters who were born with SMA Type 1.

The oldest daughter was born in 2017 and diagnosed at 8 weeks after severe respiratory complications. She was referred to Dr. Castro and began treatment with the only therapy available – SPINRAZA.

“Although the medication was slowing disease progression, her airway was still collapsing and, at 5 months of age, she needed a tracheostomy and G-tube,” Dr. Castro says.

When the parents were expecting their second daughter in 2019, Dr. Castro provided a testing kit for the obstetrician. The younger sister received a positive SMA result when she was just 5 days old. She began treatment with ZOLGENSMA, the gene transfer therapy, at 10 days of life.

Today, the younger sister is 2 years old and never required a tracheostomy. She sits, supports her head and body, eats by mouth and talks.

“Along with the medication she received, we also have physical and occupational therapists who work with her to improve motor function,” Dr. Castro says. “We’ve made amazing progress so far and it’s quite possible she will walk in the future. Patient stories like this drive us to continue to be on the leading edge for SMA, as well as other rare genetic disorders, so we can diagnose and treat children at the genetic level and ensure happier, healthier futures.”

Learn more about innovative care for neuromuscular disease at Children’s Health >>