• Zolgensma, a formulation of onasemnogene abeparvovec-xioi, is a type of gene therapy that can help improve spinal muscular atrophy (SMA) in children.
• Researchers previously thought that adult immune systems were more likely to interfere with this treatment, which would prevent it from working properly in that age group.
• Now, a new study shows that the treatment may be more effective for adults than previously believed.

A treatment option for childhood SMA called Zolgensma may work better than expected in adults with the condition, according to a new study. A formulation of onasemnogene abeparvovec-xioi, Zolgensma is a groundbreaking gene therapy treatment approved by the U.S. Food and Drug Administration (FDA) in 2019 for children under 2 living with SMA.

Previously, researchers thought immune systems in adults with SMA would interfere with the drug. New research suggests, however, that these assumptions were incorrect. The findings could open the door for clinical trials of Zolgensma on adults with SMA.

The new research was published on Sept. 16 in the journal Human Gene Therapy.

How Does Zolgensma Work?

Researchers previously assumed that onasemnogene abeparvovec-xioi wouldn’t work well in adults due to the way it’s delivered into cells. Gene therapy is the process of adding a new gene into cells. People with SMA don’t have a working copy of a gene called survival motor neuron 1 (SMN1), and onasemnogene abeparvovec-xioi helps provide cells with a functional SMN1 gene.

Typically, gene therapy uses an inactive virus to deliver the gene to cells. Through onasemnogene abeparvovec-xioi, a virus engineered to contain the SMN1 gene can get inside neurons (nerve cells). The neurons can then use the gene to make SMN protein, which helps reduce SMA symptoms and improves a child’s ability to move. The virus doesn’t typically harm the cells or cause infections.

Why Wasn’t Zolgensma Tested in Adults?

Onasemnogene abeparvovec-xioi is made from parts of a virus called adenovirus. These viruses can cause conditions like the common cold, other respiratory infections, or diarrhea.

The older you get, the more likely you are to be exposed to this virus. When you have an adenovirus infection, your immune system makes antibodies (immune system proteins) that help fight off the virus. These antibodies stick around so that they can more effectively destroy the virus if you come into contact with it again. Therefore, people are more likely to have adenovirus antibodies as they age.

Researchers have previously assumed that onasemnogene abeparvovec-xioi wouldn’t work as well in adults. They theorized most adults would have enough adenovirus antibodies to fight off the treatment and prevent it from getting into cells. Thus, Zolgensma was tested only in infants and very young children.

What Does the New Study Show?

Researchers wanted to test whether their assumptions were correct and measure adenovirus-fighting antibody levels in adults. Although previous studies have found that most adults have these antibodies, researchers hadn’t previously analyzed these proteins in adults with SMA.

The authors of the new study looked for anti-adenovirus antibodies in 69 people with SMA type 2 or 3. They found that only three of these individuals — less than 5 percent — had high antibody levels. Most people in the study didn’t have enough antibodies to neutralize the gene therapy.

The researchers concluded that onasemnogene abeparvovec-xioi may be worth testing further in adults. They wrote that the virus used to make this treatment “might be suitable for gene therapy in adult patients with SMA, regardless of patient age, sex, SMA type, walking ability, or ventilatory status.”

Importantly, the drug hasn’t been tested in adults. Researchers use clinical trials to determine whether a treatment works and whether it’s safe. People with SMA may be able to participate in trials to help researchers come up with better treatment plans or to access new therapies that may work better.

Clinical trials are underway to explore possible new therapies and discover new uses for existing treatments. Researchers are still learning more about SMA and making treatment advances.