The gene therapy drug onasemnogene abeparvovec-xioi (Zolgensma) replaces the missing or nonworking SMN1 gene involved in SMA type 1, which can improve life expectancy and motor function.

Spinal muscular atrophy (SMA) is a rare genetic disease that progressively affects motor neurons in the spine and brainstem. It leads to weakness of voluntary muscles, which can affect body functions, including:

  • speaking
  • eating
  • walking
  • breathing

Infants and children typically receive a SMA diagnosis through genetic testing or newborn screening. As noted in a 2019 article from the American Academy of Pediatrics, it’s the most common inherited cause of childhood mortality.

There are four main types of SMA, each defined by the age of onset:

  • type 1
  • type 2
  • type 3
  • type 4

According to the Muscular Dystrophy Association, children who display symptoms at birth or during infancy often have type 1 SMA, which significantly affects motor function. The earlier symptoms begin, the greater the effect.

However, an innovative gene therapy approved in May 2019 to treat children under age 2 is providing hope for families affected by SMA.

Onasemnogene abeparvovec-xioi (brand name Zolgensma) is the first gene therapy approved to treat children living with SMA.

In May 2019, the Food and Drug Administration (FDA) approved Zolgensma, a single-dose intravenous therapy that targets the cause of SMA.

Specifically, Zolgensma is indicated for children 2 years old and younger without end-stage weakness.

The single-dose gene therapy is given as a one-time infusion into the vein using an IV. The procedure takes several hours, with the infusion running for 60 minutes.

After the infusion, the healthcare team will monitor your child for 2 hours. Both during the infusion and after, your child’s vitals will be monitored. Follow-up appointments that include lab tests are required for up to 1 year.

SMA affects the motor nerve cells in the spinal cord. This disease is caused by an inherited faulty SMN1 gene. This causes children to have problems holding their heads up, breathing, and swallowing.

Mutations caused by the SMN1 gene are classified based on the age of onset and severity, with the most common and severe being infantile-onset SMA. Many children affected by type 1 SMA don’t survive past early childhood.

The one-time-only dose of Zolgensma targets the genetic root cause of SMA and replaces the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene. This helps the motor neurons work properly.

It’s important to note that Zolgensma doesn’t change or become part of the child’s DNA.

Researchers indicate that the earlier children receive spinal muscular atrophy gene therapy, the better the results. Children who get this one-time intravenous administration of Zolgensma may notice an improvement in muscle movement and function.

Clinical trials also show a decreased need for respiratory support and an improvement in survival rate. Trials haven’t focused on children with advanced SMA.

The FDA reports that the safety of Zolgensma is based on both ongoing and completed clinical trials studying a total of 36 pediatric patients with infantile-onset SMA.

According to the data, the most common side effects of Zolgensma are elevated liver enzymes and vomiting.

Children with a preexisting liver impairment face an increased risk for serious liver injury if treated with Zolgensma. Because of this, liver function should be assessed prior to treatment and monitored for a minimum of 3 months after treatment, according to safety information from Novartis.

Thorough screening and careful post-gene transfer management are critical to the safety and effectiveness of replacement therapy with onasemnogene abeparvovec-xioi.

Experts are hopeful about the future of SMA gene therapy.

According to a 2020 study published in the journal Pediatrics, safety and early outcome from the first 21 children (ages 1 to 23 months) treated in Ohio shows that gene transfer was well tolerated in children 6 months old and younger.

Older children, however, experienced higher elevations in aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase, which required a higher dose of prednisolone.

Overall, researchers believe the results of the study are promising. More specifically, they report that symptomatic patients experienced functional improvements in motor functioning, both subjective and objective.

What’s more, researchers also report that five children treated prior to symptom onset didn’t develop the signs of weakness typical of SMA.

One concern to note is the high cost of the drug. Zolgensma reportedly costs $2.125 million for a single dose. Additionally, Zolgensma in patients with advanced SMA hasn’t been evaluated.

There are still ongoing clinical trials testing the efficacy and safety of Zolgensma in various patients, representing different ages and SMA types.

Considering the recent approval for use and high cost of Zolgensma, continued research is needed. At this time, approval for use is also limited to those under 2 years of age.

Other FDA-approved treatments currently used to treat SMA include nusinersen (Spinraza) and risdiplam (Evrysdi).

Nusinersen is approved for all ages and types of SMA. It’s an intrathecal injection, meaning it’s injected into the spinal fluid and must be administered by a healthcare professional. Dosage involves four injections over the first 2 months, followed by maintenance doses every 4 months.

Risdiplam is approved for those 2 months of age and older. It’s a daily oral medication taken at home.

There are other treatments still being researched.

Can SMA be cured with gene therapy?

Zolgensma is a one-time gene intravenous therapy that targets the genetic cause of SMA by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene.

This helps the motor neurons work properly and typically results in improved outcomes.

Does Zolgensma cure SMA completely?

Zolgensma replaces the function of the missing or nonworking SMN1 gene with a working copy of the SMN gene, which can improve life expectancy and motor function.

But it’s not considered a cure, as it does not reverse any of the effects of SMA from before therapy and because children may continue to have SMA symptoms after receiving a dose.

What is the life expectancy of a type 1 SMA gene therapy patient?

As Zolgensma was approved in 2019, long-term data on life expectancy is not yet available.

However, according to follow-up data from 2023 on the children involved in two phases of clinical study on the drug, all participants were alive 7.5 years later. Some gained motor milestones, such as crawling or sitting unassisted.

Is SMA approved by the FDA for gene therapy?

The gene replacement therapy drug onasemnogene abeparvovec-xioi (Zolgensma) is approved to treat type 1 SMA in children under 2 years of age.

Spinal muscular atrophy is a rare but serious genetic disease that affects the peripheral nervous system, central nervous system, and voluntary muscle movement. Children with type 1 SMA face a greater effect on motor function.

Results from ongoing clinical trials show promising improvements in the quality of life for those affected by SMA, thanks to gene replacement therapy.

For more information about single-dose gene replacement therapy for spinal muscular atrophy, talk with a doctor.