2 Given Spinraza as Newborns Still Showing Normal Development
Two children genetically diagnosed with spinal muscular atrophy (SMA) before birth and starting treatment with Spinraza (nusinersen) within the first days of life have shown normal motor development, including a girl who is now almost 6 years old, a study reports.
The girl was likely to develop SMA type 2, a milder form, while the other child, a boy, likely had the severe type 1 disease. By age 13 months, he had achieved all age-appropriate motor milestones, including walking without assistance.
These cases — representing the earliest initiation of Spinraza reported to date — further support the importance of initiating SMA-specific treatment as early as possible, preferentially shortly after birth, to achieve the best outcomes, the researchers noted.
The study, “The outcome of two SMA cases treated with nusinersen at seven hours and at three days of life: the earliest ever,” was published in the journal Neuromuscular Disorders.
Three disease-modifying therapies (DMTs) for SMA have become available in the past decade, revolutionizing the disease’s therapeutic landscape. While they have distinct mechanisms of action, they all work to increase the levels of SMN — the protein essential for muscle health that is missing in people with SMA due to mutations in the SMN1 gene.
It is well-established that clinical outcomes are better when treatment is initiated as early as possible, with the best outcomes typically seen before symptom onset. As such, increasing efforts are focused on the implementation of prenatal testing and newborn screening for SMA around the world.
A team of researchers in Turkey describe what they believe to be two cases of the earliest initiation of Spinraza reported to date. A boy and a girl were diagnosed before birth due to a history of SMA in the family, and both were treated within the first three days of life.
Biogen’s Spinraza was the first DMT approved for children and adults with all SMA types. It is administered directly into the spinal canal at a recommended regimen of four initial loading doses, followed by maintenance treatment every four months.
The boy was the third child born to first-cousin parents, whose two previous children died within their first six months of life due to SMA type 1. In the absence of treatment, this severe form typically results in swallowing difficulties, an inability to meet early motor milestones, and in the need for permanent ventilatory support or death by the age of 2.
At three months of gestation, genetic testing revealed that the boy also had SMA, most likely type 1 disease, due to the presence of two copies of the “backup” SMN2 gene — with higher copy numbers being associated with milder disease.
While he was alert and showed spontaneous arm and leg movements with normal muscle tone after birth, his deep tendon reflexes, such as the reflex that occurs when a person’s knee is tapped, were absent — one of the earliest signs of SMA type 1.
Spinraza was administered at seven hours post-birth. A neurological exam at 40 days (after the four loading doses of treatment) was completely normal, including in terms of deep tendon reflexes, which were restored.
Up to 13 months of age, the time of the latest assessment, he had achieved motor milestones within the normal age range of unaffected children, including the ability to control his head, crawl, and sit, stand, and walk without support.
He never showed swallowing difficulties, was following a normal growth curve, and had not been hospitalized due to lung infections, which are a common complication of type 1 disease. Muscle and neurological tests remained normal.
The girl was diagnosed with SMA at 11 weeks of gestation and carried three SMN2 gene copies, similar to her 6-year-old sister who had SMA type 2, a milder form characterized by the inability to walk without support.
Since the girl had no symptoms after birth, she met the inclusion criteria of the global, Phase 2 NURTURE clinical trial (NCT02386553), which is evaluating the safety and effectiveness of Spinraza in 25 newborns, up to 6 weeks old at enrollment, genetically diagnosed with SMA but not yet showing symptoms.
Upon her parents’ consent, she was enrolled in the trial and received the first Spinraza dose at three days of life, never missing a dose up to nearly 6 years of age, the time of her latest assessment within NURTURE.
“This girl has had a remarkable evolution,” the researchers wrote, adding that “she has consistently demonstrated normal results on physical and neurological examination, with preserved deep tendon reflexes.”
Her growth has been completely normal, meeting motor milestones within the normal age range and now being able to run as well as her healthy peers in preschool.
The boy and girl will continue to be followed by the researchers.
These children, likely representing the “earliest ever treated SMA cases,” showed a normal motor development, “indicating that initiating treatment immediately after birth, as in these cases, is essential for a good outcome,” the scientists wrote.
“The treatment options for [a]ffected babies should be discussed with the family in depth, and naturally this has to be done at a very early stage, preferably not beyond the newborn period,” they added.
The team noted that these cases further support the widespread implementation of prenatal and newborn screening programs to initiate SMA treatment as early as possible and optimize these babies’ chances of growing and developing as unaffected children.