ATP Series

SMA: What's Next?

How Treatments for Spinal Muscular Atrophy Could Impact Mobility

• By Laurie Watanabe
• Dec 01, 2021

The last time Cure SMA — a national organization that supports people with spinal muscular atrophy (SMA) and their families — held its annual conference in person was June 2019.

Spirits were high at that event in Anaheim. For the first time, there were two approved treatments for SMA, which is the most common genetic cause of death in infants worldwide. Spinraza (nusinersen), the first SMA drug therapy and one that requires ongoing administration, had been joined by Zolgensma, a one-time gene therapy treatment administered by intravenous infusion.

Kenneth Hobby, Cure SMA’s Executive Director, spoke of new horizons for the adults (Spinraza) and children (Spinraza and Zolgensma) taking the treatments.

“It’s not going to be the SMA we’ve known in the past,” Hobby told conference attendees. “In some ways, SMA is going to be new. New issues are going to be created.” He suggested that SMA symptoms might get milder as a result of the treatments, but that some issues — such as significant scoliosis — would likely remain.

The Pandemic’s Effect

The pandemic that has prevented in-person conferences for Cure SMA the last two years also made it more difficult for some SMA patients taking Spinraza to access those treatments on time. In addition, pandemic lockdowns made it more difficult for some patients to regularly receive physical therapy.

A September 2021 study published in Frontiers in Neurology examined the functional impact when children’s nusinersen doses were delayed (after four initial loading doses, nusinersen is administered three times per year). The study — Effect of the COVID-19 Pandemic on Children with SMA Receiving Nusinersen: What Is Missed and What Is Gained? — was led by Italian researchers who studied data on 25 children, aged 2 to 15, who were on a Spinraza regimen when the pandemic began.

Marisa Wexler, MS, writing for SMA News Today, said eight of the children experienced delayed Spinraza infusions due to pandemic lockdowns, with those postponements ranging from 26 to 91 days. Researchers “noted that there was no clear association between these treatment delays and changes in functional scores,” Wexler said, though a 14-year-old patient who experienced a 59-day delay in receiving the nusinersen dose did show “a marked worsening of scoliosis,” the research said.

Researchers did evaluations after the children received their second infusion treatments during the pandemic lockdown; the second infusions were not delayed and were given four months after the previous infusions. Researchers found that 10 patients (40 percent) “showed a reduction in the functional score, whereas eight patients (32 percent) showed an improvement.”

Study results suggested that caregiver support significantly impacted the children’s functional scores in at least some cases. The children with the greatest reductions in functional scores were a patient who’d experienced the 59-day infusion delay and presented with significantly worsened scoliosis; a patient with “a single and fatigued parent as a sole caregiver”; and a patient “with a difficult social situation and parents who experienced depression due to loss of their jobs.”

Parents were asked about changes in their children’s muscle strength, swallowing and breathing functions. Forty percent of parents whose children experienced loss of function said those changes “are mainly due to the suspension of outpatient physiotherapy,” while 24 percent of parents said their children’s loss of function was due to delays in receiving nusinersen.

Researchers concluded that a child’s support system at home during the pandemic lockdown was crucial. “Children who had both parents caring for them and helping each other during the lockdown showed the best improvement in motor function, while in the presence of social issues, above all in single-parent families, children suffered a lack of home institutional help,” they said. “The great worsening [in function] was seen in both the shortand long-term evaluations and cannot be attributed to the delay in infusions but to a difficult family situation of the patients.”

A Third Treatment Is Now Available

In August 2020, the U.S. Food & Drug Administration approved Evrysdi (risdiplam) to treat adults and children with SMA who are at least 2 months old. An Aug. 7, 2020, announcement by Cure SMA said the treatment “showed clinically meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA.”

Evrysdi works “by helping to make and maintain more SMN protein,” according to Genentech USA, the manufacturer. It’s taken once daily in liquid form orally or through a feeding tube, and it’s currently the only treatment taken at home.

Genentech reported that 41 percent of infants with Type 1 SMA who took Evrysdi for 12 months could sit unassisted for at least five seconds — an ability not expected in untreated infants with Type 1 SMA. After 24 months on Evrysdi, 59 percent of the children could sit unassisted for at least five seconds.

After 12 months on Evrysdi, 90 percent of infants were alive and breathing without permanent support, Genentech said. After 23 months on Evrysdi, 81 percent of the children were alive and breathing without permanent support.

Children and adults with Type 2 or 3 SMA demonstrated improved motor function after taking Evrysdi for 12 months, Genentech said. The patients on Evrysdi also showed improved upper-extremity function.

What to Expect Next

It will take some time to see how treatments will impact the personal mobility of people with SMA. But a study in Poland published in August 2021 offers insight into what they could experience.

Motor Function of Children with SMA1 and SMA2 Depends on the Neck and Trunk Muscle Strength, Deformation of the Spine, and the Range of Motion in the Limb Joints was published Aug. 30, 2021, in the International Journal of Environmental Research and Public Health. Researchers examined 27 children, ranging from 6 months to 15 years. Nineteen children had SMA Type 1, and eight had SMA Type 2. All participants were receiving drug treatments for SMA at the time of the study. Researchers examined the children’s motor function, range of motion, posture, and neck and trunk muscle strength.

“The results of this study show a strong relationship between motor function and the size of the scoliosis, severity of chest deformity, and oblique position of the pelvis,” researchers said. “Spine deformity, and the accompanying changes in the structure of the chest and the position of the pelvis, was also correlated with the measurements of the strength of the muscles of the neck and trunk. Significant correlations between muscle strength, the deformation of the chest, and the oblique position of the pelvis have been demonstrated in children able to sit independently.

“The results indicate that the development of scoliosis in SMA patients adversely affects the motor function, range of motion, and muscle strength values and may influence quality of life. … Due to numerous disorders associated with deformation of the spine, preventing the development of scoliosis and the accompanying changes in the musculoskeletal system should be considered one of the main goals of treatment of children with SMA.”

Researchers suggested that an SMA patient’s mobility will ultimately depend on far more than a drug treatment’s success.

“The deterioration or lack of improvement in the functional status of a child does not have to result from the ineffectiveness of the pharmacological treatment used, but it may result from the progression of scoliosis, intensification of chest deformities, or increasing contractures,” the study said. “It is important to systematically assess the musculoskeletal system and to implement early prevention aimed at preventing scoliosis and contractures, as well as training to strengthen the muscles.”

This article originally appeared in the Nov/Dec 2021 issue of Mobility Management.