Type II and III SMA: A Promising New Gene Therapy

In SMN1-related spinal muscular atrophy (SMA), the currently available gene therapy, Zolgensma, administered as a single intravenous infusion, is indicated in young children weighing less than 21 kg with type I SMA or in presymptomatic patients with up to three copies of the SMN2 gene.

A Chinese team has developed another gene therapy, GC101, which, like Zolgensma, aims to deliver a functional SMN1 gene to induce production of the SMN protein. This new therapy was evaluated as an intrathecal injection in an open-label trial involving six patients with type II SMA and three patients with type III SMA, aged six months to 18 years. These forms are less severe and have a later onset; however, in the absence of treatment, motor function deteriorates as the disease progresses.

Patients were followed for one year after the single intrathecal injection of the treatment. Motor function improved or remained stable in all patients, and no serious treatment-related adverse events were reported.

With this new treatment, the two patients who were able to walk showed improvement in gait, and one of them was able to jump at the end of follow-up. In addition, the five patients whose motor function had declined regained motor abilities, including movements enabling them to crawl. For example, one patient was once again able to stand unaided after eight months of treatment.

The researchers also observed that the earlier the treatment was initiated, the greater the improvement in motor function. Further trials involving a larger number of patients are now required to confirm the safety and efficacy of this treatment.

Source
Single-dose GC101 gene therapy for spinal muscular atrophy types II and III: an open-label single-arm study
Ma XW, Jiang XY, Li ZQ et al.
World J Pediatr. 2025 Sep.