An infant with type 0 spinal muscular atrophy (SMA), a severe disease form evident before birth, began treatment with Spinraza (nusinersen) at 2 weeks old and showed mild improvement, but died of cardiac arrest months later.
Published in Annals of Clinical and Translational Neurology, the report is titled, “Nusinersen in type 0 spinal muscular atrophy: should we treat?“
SMA is caused by mutations in SMN1 gene, which codes for the protein SMN that’s essential for muscle health. Another gene, SMN2, can code for limited SMN production, and fewer SMN2 copies are associated with more severe disease.
Spinraza, developed by Biogen, is an approved SMA therapy that works by increasing the amount of SMN protein that cells can make from the SMN2 gene.
Type 0 SMA is diagnosed when this disease manifests while a baby is still in the womb. It is the most severe form of SMA, and almost always fatal within the first months of life.
Researchers in Italy described the case of a male infant with type 0 SMA, born to parents whose previously child also had SMA type 0 and died about three weeks after birth.
Genetic testing of the fetus at 20 weeks revealed SMN1 mutations, and one SMN2 copy (two copies are typically found in children with SMA type 1, also a severe form). The pregnancy was marked by reduced fetal movements.
Substantial muscle weakness and a lack of sucking and swallowing reflexes were found on examination; additional genetic testing confirmed the earlier results. Heart imaging revealed some cardiac defects.
Because Spinraza is a fairly new therapy — it was first approved in December 2016, becoming the first disease-modifying treatment for SMA — and type 0 SMA is especially rare, almost no published data on the use of Spinraza or other SMA treatments in these patients are known.
“The clinicians felt that it [Spinraza treatment] was unlikely to see a significant effect in a type 0 patient,” the researchers wrote, noting that guidelines issued in 2018 also suggested “that treatment should not be started in symptomatic type 0 patients.”
The baby’s parents were informed of these concerns, but decided to begin Spinraza treatment for their newborn.
“The choice of starting [Spinraza] in our case was very controversial and required the involvement of our ethics board,” the researches added. It was allowed because “possible improvement with prolonged survival could not be excluded a priori.”
The baby started on Spinraza 13 days after his birth. About two months later — after three doses of the medication — “mild” improvements were observed in movement and breathing ability.
At 3 months old, the infant underwent surgery to allow feeding via a tube. But a month later, his heart function began to progressively deteriorate.
The infant died of a sudden heart attack at 5 months old.
“We report a case of type 0 SMA with one SMN2 copy, treated with Nusinersen. The clinical course following treatment with Nusinersen revealed some mild improvement, generally not observed in type 0,” the investigators wrote.
Despite “minimal improvement on mobility and, to some extent on respiratory function,” however, “the effect was not enough to contrast the overall severity and the multisystemic involvement” of this severe SMA form, they added.
“[R]ecurrent infections, and a deterioration of cardiac function resulted in a cardiac arrest at the age of 5 months.”
The research team concluded with the hope that this report, in addition to two others on treating type 0 infants, “will … be of help for families and clinicians with a new diagnosis of type 0 at the time of considering the opportunity of treatment.”
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