Media release

From: Springer Nature

Health: Single-dose treatment improves symptoms of spinal muscular atrophy

A single-dose gene replacement therapy is found to improve movement ability in children over 2 years of age and teenagers with spinal muscular atrophy, according to research published in Nature Medicine. The results of this phase 3 clinical trial, involving 126 children and adolescents, could support an alternative to lifelong, repeat-dose treatments for people living with spinal atrophy beyond the age of 2 years.

Spinal muscular atrophy is a rare genetic condition that causes muscle weakness and loss of movement over time. It develops because the body cannot make enough of a protein, called survival motor neuron, needed for healthy nerve cells. Onasemnogene abeparvovec is a gene therapy that restores production of this missing protein in a single treatment. However, it is currently approved in the US and Europe only as a single intravenous treatment for children under 2 years of age. Therefore, those older than 2 years of age can receive treatments only to slow the disease, and these must be taken regularly, either by injection or orally.

Richard Finkel and colleagues assessed the safety and efficacy of a single dose of onasemnogene abeparvovec delivered directly into the spinal fluid of children older than 2 years of age with spinal muscular atrophy. The year-long trial involved 126 children and adolescents between 2 and 18 years of age who were able to sit but had never walked on their own. The participants were randomly assigned to receive either the gene therapy (75 participants) or a placebo (51 participants). Those who received the active therapy achieved a significantly greater improvement in motor function scores on a validated test (which identified gains in 33 specific skills, such as moving from a lying into a sitting position, walking, and climbing stairs) compared with those who did not. Side effects were similar in both groups and were generally manageable.

The findings suggest that this one-time treatment is effective in participants older than 2 years of age when delivered directly into the spinal fluid. Furthermore, they support broadening access to this gene therapy for spinal muscular atrophy to patients beyond infancy, addressing an unmet need in older children and adolescents. However, the study lasted only 12 months, so longer-term monitoring is needed to confirm long-term safety and efficacy.