A New Drug for Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a rare genetic pediatric condition that affects muscle function throughout the body.

“Before treatments were available, the spinal motor neurons — the main neurons coming out of the spinal cord — would disintegrate and fall apart over time,” says pediatric muscular disease expert Anne Stratton, MD.

As a result, patients with SMA can experience progressive muscle weakness, mobility challenges and eventual difficulty swallowing and breathing. The carrier frequency for SMA is about one in 54, making it the second most common autosomal recessive condition behind cystic fibrosis, though only about 1 in 8,000 children are born with the disease.

There are four types of spinal muscular atrophy (SMA). The most severe forms of SMA affect patients in infancy; they may move less in the womb and weakness is apparent within the first few days to months of life. Until several years ago, there was no treatment for SMA, and patients with the most severe form of the SMA disease would die of respiratory failure by age 2.

Risdiplam brings hope for spinal muscular atrophy

The devastating impact of SMA began to change course in 2017 when a new FDA-approved drug that can help increase the body’s production of the critical survival motor neuron (SMN) protein became commercially available to neuromuscular doctors nationwide.

While the drug proved effective at halting the progression of SMA, it didn’t reverse the loss of motor neuron function that had already occurred.

"In the most severe form, you start losing muscle function in the first months of life and eventually become paralyzed,” Dr. Stratton says. “You can't even swallow or breathe.”

This showed Dr. Stratton and other providers in her field that early treatment was key to preventing the disease’s most challenging symptoms. Now, there’s a nationwide recommendation that all states provide both parents with the option to screen for this condition during pregnancy.

This is what transformed outcomes for a pregnant patient in Brush, Colorado. The family opted for the SMA screening because the pregnant parent had a cousin who died from the most severe form of the disease and suspected she might be an SMA carrier.

Testing showed that both parents had mutations in the SMA gene, which meant that the baby had a 25% chance of having the disease. Moreover, due to the parents’ family history, it would be the most severe type.

Genetic testing in utero

After the couple was determined to be carriers of the SMA gene, they were tested for the condition via amniocentesis, a type of prenatal genetic testing where providers test a small sample of amniotic fluid. Amniocentesis helps check for a variety of genetic conditions beyond spinal muscular atrophy, such as Down syndrome.

When the family’s genetic testing in utero proved that the child indeed would be born with the most severe type of SMA, they were referred to Children’s Hospital Colorado, where Dr. Stratton and her team set a plan into motion.

“Knowing that the baby could be born with symptoms and have respiratory distress at birth and need a higher level of care, we recommended that the baby be born at a tertiary care center,” Dr. Stratton says.

The team consulted with the family’s obstetrician to discuss maternal and fetal safety, and risks and benefits of induction. It was decided to induce labor at 38 weeks and 2 days, with plans to administer the drug on the child’s first day of life.

Planning the delivery this way ensured that the baby wouldn’t be born in the family’s rural hometown, which didn’t have the resources the baby might need upon birth. It also lessened the time for disease progression in utero and ensured the drug could be given immediately, since prenatal delivery of the drug hasn’t yet been approved.

The future of SMA treatment

There are multiple treatment options for patients with SMA now; however, the family opted for the oral treatment with risdiplam because it was the most accessible, with just a daily squirt in the child’s mouth for life. Now, at six months of age, the child remains symptom-free.

“This was definitely our best success of 2024," says genetic counselor Melissa Gibbons, MA. “She's kind of the model of what we would like that prenatal program to look like from a treatment standpoint.”

Children’s Colorado has more patients with SMA identified on newborn screening than many other institutions across the country, in part due to the fact that we have the only neuromuscular center serving all of Colorado and Wyoming. Seeing more cases has allowed the program to hone its expertise and expand its scope.

“I think there's a lot of systems that have come together perfectly over the last five years that have really made it so that we can have stories like this,” Gibbons says. “That is not necessarily commonplace across the country, so I think this program does speak really nicely to Children's Colorado and our collaboration with outside providers.”