Feeding Problems May Persist in Type 1 Children, Despite Spinraza Use

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by Marta Figueiredo PhD |

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Despite its well-reported benefits in motor function, Spinraza (nusinersen) may not be as effective at preventing or easing feeding and swallowing difficulties in children with spinal muscular atrophy (SMA) type 1, according to a single-center study in the U.K.

Those with SMA type 1c, this type’s least severe subgroup, were more likely to maintain an ability for exclusive oral feeding after two years of Spinraza treatment.

While most of the children already showed severe feeding issues at the time of Spinraza initiation, these findings suggest that type 1 patients remain vulnerable to feeding and swallowing problems despite Spinraza’s use, highlighting an unmet clinical need.

The study, “Evolution of bulbar function in spinal muscular atrophy type 1 treated with nusinersen,” was published in the journal Developmental Medicine & Child Neurology.

SMA is caused by low to no levels of the SMN protein, leading to the progressive loss of motor neurons, the specialized nerve cells that control voluntary movement, and resulting in muscle weakness and wasting.

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SMA type 1, the most common and second most severe disease type, is associated with a life expectancy of less than two years if left untreated.

It is classified into three subgroups according to the age at symptom onset: within the first 2 weeks of life (type 1a), by 3 months of age (type 1b), and between ages 3 and 6 months (type 1c). Earlier onset is associated with more severe disease.

In children with SMA type 1, progressive muscle weakness and wasting affect not only their motor function, but also their ability to breathe and eat. Notably, feeding issues are related to problems with bulbar muscles, those that control speech, swallowing, and chewing.

While the emergence of disease-modifying therapies such as Biogen’s Spinraza has significantly improved motor and lung function, as well as survival, data are still limited on the trajectories of swallowing and feeding difficulties in type 1 infants given such therapies.

“This is due to both the lack of validated tools to assess swallow function in SMA1 [SMA type 1] and to the limited availability of longitudinal data,” the researchers wrote.

A team of researchers in the U.K. retrospectively analyzed the evolution of bulbar function in 24 children (14 girls and 10 boys) with SMA type 1 who were treated with Spinraza for at least two years between 2017 and 2020 at a single center in London.

Spinraza is given directly into the spinal canal to reach the brain and spinal cord, where motor neurons are located.

To assess bulbar function, the researchers modified the Functional Oral Intake Scale — which assesses change in functional eating abilities in adults with stroke — so that it could be used in children.

Scores for the adapted scaled, named the Pediatric Functional Oral Intake Scale (pFOIS), ranged from one to six. One indicates a lack of functional eating abilities and total dependence on tube feeding, and six represents total, age-appropriate, oral intake with no restrictions.

After being validated in infants through 16-year-olds with bulbar function-affecting health conditions, pFOIS was used to assess patients’ bulbar function at Spinraza initiation and after six, 12, and 24 months. Changes in motor skills, as well as in the need for ventilatory and feeding support, were also assessed.

Half of the children had type 1c, nine had type 1b, and three had type 1a. Their median age at Spinraza initiation was 11 months (range, 1 month to 7 years). All started treatment after symptom onset, and at this time, 14 of them (58.3%) were already using a feeding tube. Median age at tube feeding initiation was 8 months (range, 0–2 years).

After two years of Spinraza treatment, the number of children needing a feeding tube had risen to 20 (83.3%). This group included all children with SMA types 1a and 1b, and eight of the 12 with type 1c.

The remaining four type 1c children maintained their feeding skills and continued to be exclusively fed via oral route, suggesting that those with the least severe form of SMA type 1 may be “more likely to maintain bulbar function,” the researchers wrote.

Their median p-FOIS score was three at treatment imitation and two after one and two years, “reflecting worsening or lack of improvement in bulbar function,” the team added.

Six children showed gains in their p-FOIS score, but the observed one-point increase “does not reflect a substantial functional change in swallowing, as all remained tube fed,” the researchers added.

While earlier SMA treatment has been reported to result in better outcomes, initiating Spinraza at a younger age (younger than 6 months; seven children) was not associated with greater benefits in bulbar function.

However, all of these seven children had the most severe forms of type 1 (subtypes a and b), “so it is difficult to draw clear conclusions,” the researchers wrote.

No child was treated with Spinraza before symptom onset; this approach has been previously associated with preserved swallowing skills.

Notably, while feeding/swallowing difficulties were either generally maintained or worsened in these children, their motor function showed pronounced improvement after two years of treatment.

These findings highlight that SMA type 1 children remain vulnerable to bulbar difficulties despite Spinraza’s use, “in contrast to the improvement in motor abilities” that is consistent with data from previous studies, the team wrote.

“Awareness of persistent feeding difficulties in [Spinraza-treated] patients with SMA1 helps guide discussions with families, including prognosis and treatment, as well as informing healthcare resource allocation and standards of care,” the researchers added.

Longer follow-up studies in larger patient groups are needed to confirm these findings.

Spinraza’s limited efficacy on bulbar function may be related to its administration route, the team noted, as lower SMN levels were previously reported in motor neurons controlling bulbar muscles relative to other motor neurons in Spinraza-treated type 1 infants.

As such, whole body-distributed approved SMA therapies, like Novartis’ Zolgensma that is given directly into the bloodstream and Roche’s oral therapy Evrysdi (risdiplam), “could be more effective in preserving bulbar function,” the researchers wrote.

“However, longitudinal real-world data will be needed to evaluate whether this corresponds to a clinical benefit for treated patients,” they added.

Study data also suggest that p-FOIS may be a tool to monitor bulbar function and treatment response in children with SMA. Again, larger studies are needed to confirm its potential.