Early SMA treatment safe, effective for preterm baby boy in Canada
Risks and benefits of early treatment for preemies must be weighed, report says
For a boy with spinal muscular atrophy (SMA) who was born prematurely, treatment with Spinraza (nusinersen) until he was old enough to receive Zolgensma (onasemnogene abeparvovec) was a safe and effective therapeutic approach, according to a case report from Canada.
The infant, who had been diagnosed presymptomatically via newborn screening (NBS), ultimately reached motor milestones on a slightly delayed time course, was able to orally feed, and had no respiratory problems up to more than 1.5 years old.
Scientists believe the case study highlights the importance of balancing the need for an early start to SMA treatments with the potential safety risk of such therapies in babies who are born early.
“With the scarce evidence that currently exists, clinicians should be aware of the efficacy and safety impact of early therapy particularly in the preterm infant,” researchers wrote.
The study, “Case report: A case of spinal muscular atrophy in a preterm infant: risks and benefits of treatment,” was published in Frontiers in Neurology.
Early diagnosis, treatment linked to better prognosis
Several countries have initiated NBS for SMA in recent years, which enables babies with the inherited neuromuscular disease to be diagnosed immediately at birth, sometimes before symptoms are even evident. An early diagnosis and start to treatment is linked to motor nerve cell preservation and a better prognosis.
Three SMA therapies — Spinraza, Zolgensma, and Evrysdi (risdiplam) — are approved in the U.S. and other countries for use in babies, with the cut-off age varying by country.
However, there is a lack of data on the safety of SMA therapies in preterm infants, or babies born after less than 37 weeks of pregnancy (gestational age). A full-term pregnancy is, on average, about 40 weeks.
The steroid treatments that are given alongside Zolgensma could possibly have adverse effects on neurological development, immune function, or other organ development in these children. The U.S. Food and Drug Administration currently does not recommend its use in preterm infants younger than 40 weeks gestational age.
On the other hand, waiting to start SMA treatment could lead to the loss of motor nerve cells and the onset of SMA symptoms, the researchers noted.
With the scarce evidence that currently exists, clinicians should be aware of the efficacy and safety impact of early therapy particularly in the preterm infant.
Presymptomatic preterm infant diagnosed with SMA via newborn screening
In the recent publication, the scientists described the case of a presymptomatic preterm infant who was diagnosed with SMA via NBS in Canada. The boy was born at 32 weeks gestation when his mother went into premature labor after an uncomplicated pregnancy.
NBS screening showed the baby was positive for SMA, but physical examinations, including motor and neurological function, were normal.
After counseling on treatment options, the boy’s parents opted for Zolgensma. However, because there was a lack of evidence about the therapy’s safety in preterm babies, the doctors decided to treat him with Spinraza until he had reached 40 weeks gestational age. Evrysdi “was not yet approved in Ontario at the time of this patient’s birth but was discussed and not favored as an option to wait to treat until he was eligible,” the researchers wrote.
Spinraza is delivered via injections directly into the spinal canal. The researchers believed there was less potential for systemic side effects with this treatment than with Zolgensma, which is given as an into-the-vein infusion.
The boy thus received three doses of Spinraza every two weeks until gestational week 40. He tolerated it well, with no complications.
When the boy was 10 weeks old, he was given Zolgensma. He also received prednisone, a steroid, the day before Zolgensma and remained on it for a month, after which it was slowly tapered off.
Lab tests during this time were generally normal, with a slight increase in liver enzymes at the start of prednisone tapering that steadily normalized thereafter.
The boy achieved head control at 4 months of age and was able to walking independently when he was 1.5 years old (18 months), reflecting mild motor delays.
Boy was able to stand, walk, sit independently at 20 months
At the time of the report, he was 20 months old and could pull himself up to stand, walk, and sit independently, as well as reach for objects. He was also eating, gaining weight, and not having any breathing issues. Tests of nerve-muscle function reflected some possible dysfunction of motor nerve cells.
Overall, “it is valuable to consider early treatment even in a preterm infant,” the researchers wrote. “Opting to bridge with [Spinraza] administration … may be one method to ensuring the best outcome.”
Importantly, each individual case may differ, the scientists noted, adding that every child should be evaluated on a case-by-case basis, “until there are enough data to suggest otherwise.”
Babies with SMA may already be at a higher risk for certain complications due to organ immaturity at birth, including those involving the heart, kidneys, or liver. This could possibly put them at a greater risk of side effects from Zolgensma, but the child in this study remained generally stable after treatment.
The risks and benefits of early treatment warrant further investigation in more children with SMA, the researchers concluded.