SMA: What's Next?
How Treatments for Spinal Muscular Atrophy Could Impact Mobility
- By Laurie Watanabe
- Dec 01, 2021
GIRL PLAYING PIANO: DEPOSITPHOTOS.COM/ZARETSKA OLGA
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
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
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
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.
Laurie Watanabe is the editor of Mobility Management. She can be reached at firstname.lastname@example.org.