An early spinal muscular atrophy (SMA) diagnosis with the help of a newborn screening program, and treatment with disease-modifying therapies before symptom onset, may prevent the development of SMA symptoms, according to a new study in Italy.
The study found that children born without symptoms who started treatment shortly after their SMA diagnosis — which followed screening at birth, implemented for the first time in Italy in late 2021 — were able to reach motor milestones at the expected age. This included sitting at 6 months of age and walking at 15 months.
“The ability to diagnose SMA in its presymptomatic stages is a game changer, as it enables healthcare providers to initiate treatment strategies even before the first signs of neuromuscular weakness appear,” the researchers wrote.
Apulia, in the so-called heel section of the boot-shaped country, “emerged as the pioneer Italian region to introduce mandatory SMA screening at birth,” in December 2021, the team noted. Now, the researchers analyzed the results of this pilot program.
Their findings were detailed in “Early spinal muscular atrophy treatment following newborn screening: A 20-month review of the first Italian regional experience,” a study published in Annals of Clinical and Translational Neurology.
Newborn screening leads to SMA diagnosis, prompt treatment, for 4 infants
SMA is mainly caused by inherited mutations in the SMN1 gene that lead to low levels of the survival motor neuron (SMN) protein. This ultimately results in the loss of motor neurons — the specialized nerve cells that control voluntary movements — and to disease symptoms.
In addition to the SMN1 gene, there is an associated gene called SMN2 that also contributes to the production of SMN protein. However, a minor genetic variance in this gene leads to only about 10% of functional SMN protein production compared with SMN1. Generally, a higher number of SMN2 copies is linked with less disease severity.
The implementation of mandatory newborn screening aims to allow the identification and treatment of patients before symptom onset. Several countries have launched such initiatives, usually involving the collection of dried blood samples and genetic analysis of the SMA1 gene.
Mandatory newborn screening for SMA started for the first time in Italy at the end of 2021. In this study, researchers investigated the impact of this program on access to care and patient outcomes in the Italian region of Apulia, located in the southern peninsular section of the country.
Four patients — two boys and two girls — were diagnosed with SMA under the program. One girl had symptoms at birth, while the other three patients showed no signs of SMA at birth or during follow-up. The researchers noted that three patients had two SMN2 gene copies, and one had three copies.
The three patients with two SMN2 copies started treatment with the gene therapy Zolgensma (onasemnogene abeparvovec) between 16 and 23 days of age. The baby with SMA symptoms at birth started treatment just nine days after diagnosis.
Zolgensma is a one-time gene therapy that’s designed to deliver a working copy of the SMN1 gene using a harmless virus.
Meanwhile, the infant with three SMN2 copies started on Spinraza (nusinersen), a different type of treatment, at 20 days of age. Spinraza, the first therapy to win approval in the U.S., is designed to increase motor neurons’ ability to produce a functional SMN protein from the SMN2 gene.
3 children remained asymptomatic from birth through 17 months
All of the children were followed closely for up to 17 months of age, or nearly 1.5 years. During this time, the three patients who were asymptomatic at birth remained asymptomatic, achieving motor milestones at the expected age and reaching the maximum score in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a scale used to assess a child’s ability to perform certain motor tasks between the ages of 6 months and 1 year. The maximum score is 64.
Two children were able to walk at the age of 15 months, while one could sit without support at 6.5 months. The girl with symptoms at birth achieved head control when she was 2.5 months, and reached a CHOP-INTEND score of 35 at 3 months.
“These findings highlight … the relevance of a therapeutic window in neurodegenerative disorders, especially in those where a diagnosis can be made before symptom onset,” the researchers wrote. Having that early diagnosis allows for treatment to begin sooner, the team noted.
Early treatment may effectively reduce severe disability, providing better motor performances and improving the quality of life and the life expectancy for these patients, while also lowering costs to healthcare systems, according to researchers.
[A] proactive approach capitalizes on the potential to halt or slow down the progression of the disease, thereby improving motor function, extending survival rates and enhancing the overall quality of life for affected individuals and their families.
The team noted that “educational initiatives aimed at parents and obstetricians were deemed crucial to enhancing awareness and expediting timely actions.”
This study also revealed the importance of shortening the timeline from birth to diagnosis and treatment decisions, the scientists said.
A “proactive approach capitalizes on the potential to halt or slow down the progression of the disease, thereby improving motor function, extending survival rates and enhancing the overall quality of life for affected individuals and their families,” the team wrote.
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