Despite Taking Spinraza, SMA Type 1 Children Show Nonmotor Problems

Marta Figueiredo PhD avatar

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 nonmotor complications, such as facial deformities, feeding problems, and scoliosis, in children with spinal muscular atrophy (SMA) type 1.

Given that all these complications may affect the child’s lung function and health, they should be closely monitored to avoid further respiratory complications — the main cause of death in this patient population — the researchers noted.

These were the findings of a small Israeli real-life study, “Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients,” published in the journal Pediatric Pulmonology.

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SMA type 1 — a severe form of the disease with an onset before 6 months of age — is characterized by progressive muscle weakness and wasting that affect not only a person’s motor function, but also their ability to breathe and eat.

Respiratory failure is the main cause of death in children with type 1 disease, who, if left untreated, typically need permanent ventilation or die at a median age of 13.5 months.

While the emergence of SMA disease-modifying therapies such as Biogen’s Spinraza has significantly improved motor function and dramatically reduced respiratory failure and mortality, “data on respiratory issues are still emerging and little is known about the long-term respiratory outcomes and complications,” the researchers wrote.

In addition, treated patients may “sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function,” they added.

Now, a team of researchers at Tel Aviv University’s Dana-Dwek Children’s Hospital in Israel, analyzed the frequency and severity of three common SMA-related complications that may affect lung function in 20 Spinraza-treated children with type 1 disease.

These included facial deformities, feeding problems, and scoliosis, an abnormal and progressive sideways curvature of the spine.

Facial deformities — driven by muscle weakness and use of breathing masks at an early age, when the skull is more flexible and prone to deformity — may challenge the fitting of an appropriate mask or interface, limiting the ability to ventilate these patients efficiently.

Feeding problems, due to weakness in the muscles involved in chewing and swallowing, increase the risk of aspiration pneumonia, a lung infection that develops due to food or liquid being aspirated into the lungs.

Caused by weakness in back muscles that support the spine’s position, scoliosis can cause breathing difficulties because the lungs have less room to expand and allow for deep breathing.

The children (12 girls and eight boys) were followed for three years, beginning in January 2017 when Spinraza was approved in Israel. They all attended the SMA center of the Tel Aviv Sourasky Medical Center. Half were Jewish and half were Arabic.

Since newborn screening for SMA is not yet conducted routinely in the country, the children were diagnosed according to clinical symptoms, at ages ranging from 1 month to 1 year. Spinraza, administered directly into the spinal canal four times a year, was initiated at a median age of 13.5 months (range, 1 month to 15 years).

A total of 17 children completed three years of Spinraza treatment with 100% adherence. Two children died from respiratory failure during the first year, and another stopped treatment during the second year after experiencing brain injury due to lack of oxygen associated with massive food/liquid aspiration.

Results showed that, 16 (80%) children were already on ventilatory support at treatment initiation (baseline), and all 17 were ventilated after three years of treatment.

Facial deformities were detected in four (20%) children at baseline and in 15 out of 17 (88%) after three years. The most common facial changes included open mouth (12 patients), nasal flattening (eight patients), and extreme facial weakness (seven patients).

Facial deformities were observed regardless of the nature (invasive vs. noninvasive) and frequency of ventilatory support.

These results call for “close follow-up of these patients along with the development of objective tools for assessment of even subtle facial changes,” as well as the use of “adjustable interfaces or custom-made masks … to reduce the risk of … permanent facial deformities when continuous ventilation is required,” the researchers wrote.

At treatment initiation, only seven (35%) patients were fed orally, with the majority using feeding tubes. After three years of Spinraza treatment, all but one child (94%) were using feeding tubes.

Four children (25%) had maintained oral feeding in parallel to a feeding tube at the request of their families. They later showed clinical and radiologic evidence of aspirations regardless of food consistency and swallowing techniques, as well as aspiration pneumonia and lung collapse. They were advised to cease oral feeding.

“While preserving eating skills is important, our findings emphasize that additional research on swallowing functions in [treated type 1] patients is required, and that assessment of swallowing function and family counseling should be routinely provided to them,” the team wrote.

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Scoliosis was present in five children at baseline (25%), all of whom were receiving ventilatory support. After three years, severe scoliosis evolved in 15 of 17 (88%) patients, four of whom had undergone corrective spine surgery and three being scheduled for surgery.

All four children who underwent scoliosis surgery recovered uneventfully, with the youngest having it at 2 years of age.

“The importance of early age corrective surgery is related to the limited period when [SMA type 1] patients have sufficient lung capacity to successfully undergo such major surgery and thereby maximize their chest wall growth potential,” the researchers wrote.

These findings highlight that Spinraza-treated type 1 children “may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system,” the team wrote.

“These increasingly growing issues make it incumbent upon us to provide tight surveillance and prompt intervention in treated [SMA type 1] patients as well as coordinate expectations with the patients and their families,” they added.