The spinal muscular atrophy (SMA) gene therapy, onasemnogene abeparvovec, is safe and well tolerated when administered intrathecally, a phase 1 ascending-dose clinical trial called STRONG discovered. The trial also found that older patients given the medium dose of the treatment showed increases in Hammersmith Functional Motor Scale Expanded (HFMSE) scores, a measure of physical ability in patients with SMA.

Onasemnogene abeparvovec is already approved in the United States and other countries to treat patients aged 2 years and under with all types of SMA. It is given as a single intravenous infusion, the dose of which is based on the patient’s weight.

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For patients with milder forms of SMA whose symptoms develop later in life, the necessary dose of onasemnogene abeparvovec is greater, raising safety concerns. Intrathecal delivery could enable a fixed-dose administration and allow the treatment of patients who are older and heavier.

The STRONG trial tested the safety, tolerability, and efficacy of intrathecal onasemnogene abeparvovec in 32 nonambulatory patients with SMA, aged 6 months to 5 years, who were able to sit unaided.

Patients were divided into 3 groups to receive a single low, medium, or high dose of onasemnogene abeparvovec. 

The primary endpoints included safety and tolerability of the treatment, independent standing for 3 seconds or more in patients who received the treatment between the ages of 6 and 24 months, and the change in HFMSE score from baseline compared with that of historic controls in patients who received the treatment between the ages of 2 and 5 years.

The results showed that all patients had at least 1 treatment-emergent adverse event. One of these, transaminase elevation, was serious and related to treatment, but no deaths occurred. 

One of the 13 patients who was treated with the medium dose when they were under the age of 2 years achieved independent standing. 

After 1 year of treatment, the change from baseline in HFMSE score was significantly better than that in the SMA historic control population for patients who received the medium dose of treatment after 2 years of age.

These results were published in the Journal of Neuromuscular Diseases


Finkel RS, Darras BT, Mendell JR, et al. Intrathecal onasemnogene abeparvovec for sitting, nonambulatory patients with spinal muscular atrophy: phase I ascending-dose study (STRONG). J Neuromuscul Dis. Published online March 9, 2023. doi:10.3233/JND-221560

Study of intrathecal administration of onasemnogene abeparvovec-xioi for spinal muscular atrophy (STRONG). December 22, 2017. Updated February 16, 2023. Accessed March 24, 2023.