Individually, Zolgensma and Spinraza have each proven beneficial in treating SMA. Combining the two gene therapies, however, may be less effective in treating children living with type 1 SMA, compared to Spinraza alone, according to a recent study.
SMA is a genetic neurodegenerative disease caused by mutations in the survival motor neuron (SMN) genes. These mutations result in insufficient SMN protein, which is necessary for muscle function and movement. Without sufficient SMN protein, the muscles cannot effectively send signals for movement, and they begin to waste away.
SMA type 1, also known as Werdnig-Hoffmann disease, represents around 55 percent of all SMA cases. Symptoms of the disease are noticeable around birth or within the first few months of an infant’s life. Although there is no cure, early treatment in SMA type 1 has been shown to improve survival. Particularly, gene therapy has revolutionized treatment for the disease.
Zolgensma (onasemnogene abeparvovec) is a gene therapy approved for treating all types of SMA in children who are under two years old. It works by replacing the faulty copies of the SMN1 gene with functional ones, helping the body make more SMN protein.
Spinraza (nusinersen) is another medication approved for treating SMA. Approved for use in all ages and for all types of SMA, Spinraza acts on the SMN2 gene, resulting in more SMN protein.
While these therapies are effective on their own, the authors wanted to see if combining the two therapies would be beneficial in treating infants with SMA type 1. A previous study with five participants showed that the therapies, when combined, were generally well-tolerated. The overall effects, however, were not known.
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The study authors put together two groups of children with SMA type 1: the first group was treated with both Spinraza and Zolgensma, and the second with only Spinraza.
Seven children were in the combination group. Six of the seven children began Spinraza treatment when they were 2 months to 6 months old, then later received Zolgensma. One child received their Zolgensma treatment first, then began Spinraza treatment 18 months later. The second group, consisting of six children, received only Spinraza treatment, which started when they were 2 months to 6 months old.
The researchers measured the children’s motor skills and function using the CHOP-INTEND scoring system. Children treated with both Zolgensma and Spinraza experienced only small improvements in their motor skills and function after adding the second therapy when compared with results after receiving the first. Similar results were seen for ventilation and cough assistance.
Both the combination and Spinraza-only treatment groups saw improvement of motor function over time — especially within six months of beginning treatment. These improvements then tapered off between six to 12 months after treatment.
The authors found that the earlier treatment began, the better it worked. Ideally, treatment should begin before symptoms show, or before motor neuron loss occurs.
Overall, the authors concluded that adding Zolgensma in addition to Spinraza treatment “does not seem to provide supplementary benefits for motor function or respiratory status, but early treatment results in better outcomes.” Future studies with more participants will be needed to confirm these findings.