A one-time gene therapy administered through an injection into the spinal fluid is both effective and safe for older children with spinal muscular atrophy (SMA). This is the result of international research recently published in Nature Medicine, to which UMC Utrecht made a significant contribution. The results are promising for a group of children who previously had no access to gene therapy.
Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disease that leads to the death of nerve cells in the spinal cord. As a result, muscles become progressively weaker, causing severe issues with movement, breathing, and swallowing. Untreated, the disease is fatal.
The Muscle Disease Expertise Center at UMC Utrecht is a nationally recognized center for neuromuscular disorders. Our multidisciplinary team provides specialized care for patients with muscle diseases, trains specialists, and conducts research. We offer quick diagnostics, guidance, and treatment—often with a diagnosis and treatment recommendation within a single day. The Spieren voor Spieren Children’s Center at the Wilhelmina Children’s Hospital provides this care for children. Here, specialists work together for fast diagnostics, tailored treatment, and broad support for both the child and family. We aim to help children participate in daily life as much as possible.
For very young children with SMA, a one-time gene therapy has been available for several years: onasemnogene abeparvovec, better known as Zolgensma. This treatment is delivered via intravenous infusion. Parents appreciate that their children only receive the medication once. “It feels very different from a treatment that needs to be repeated,” says Ludo van der Pol, Professor of Neurology and head of the SMA Expertise Center at UMC Utrecht.
Unfortunately, gene therapy via an infusion is not safe for older children. The treatment uses a harmless virus to deliver the correct gene into the cells. The heavier a child is, the more medication they need. At higher doses, too many viral particles end up in the liver, which can be dangerous. This is why children older than about two years or weighing more than twenty kilograms currently cannot receive this gene therapy.
For this group, two additional medications are available: nusinersen and risdiplam. Nusinersen (Spinraza) is administered periodically via intrathecal injection. Children can take risdiplam orally every day, either as a solution or in tablet form.
This study highlights the importance of scientific research for children with neuromuscular disorders, so they too can participate in society. This is something we work on every day at the Spieren voor Spieren Children’s Center in the Wilhelmina Children’s Hospital. But research can only continue with sufficient support. For this reason, we are supporting the 3FM Serious Request initiative, which is raising funds this year for Spieren voor Spieren.
In the STRENGTH study, the research team investigated whether the gene therapy Zolgensma is safe for older children when injected directly into the spinal fluid. This was done through a single injection. The study involved 27 children with SMA, aged 2–18, across thirteen hospitals in nine countries. All these children had previously received nusinersen or risdiplam. When the medication is injected into the spinal fluid, it goes straight to the nerve cells, so the liver is barely affected. The study found that the treatment is safe. All children experienced side effects, but these were mostly mild, such as fever, cold symptoms, or vomiting. Four children experienced significant side effects, mostly respiratory infections. No child died or was forced to stop participating in the study.
For the children who were treated, the disease remained stable. “That might not sound remarkable, but for these children and their parents, it’s very important,” says Ludo. “It means they don’t lose any of their abilities.”
The results were published in the scientific journal Nature Medicine. The company Novartis is now preparing an application to the European Medicines Agency (EMA) for approval of this new treatment. In the United States, the treatment is already approved and available. In the Netherlands, it is expected to be available at the earliest in 2027, as the approval process takes a considerable amount of time.
The results were published in the scientific journal Nature Medicine. The company Novartis is now preparing an application to the European Medicines Agency (EMA) for approval of this new treatment. In the United States, the treatment is already approved and available. In the Netherlands, it is expected to be available at the earliest in 2027, as the approval process takes a considerable amount of time.
Alongside the STRENGTH study, which UMC Utrecht participated in, the STEER study was conducted. This study focused mainly on Asian children who had not yet received medications for SMA. This was often because the medications were not reimbursed in their countries. In this group, researchers observed not only that the disease remained stable, but even that the children were able to move better after receiving the gene therapy.
