SMA Newborn Screening Improves Outcomes in New York State Data
Presymptom diagnosis and early gene therapy called an urgent need
Newborn screening for spinal muscular atrophy (SMA) leads to better outcomes, with babies being diagnosed earlier and with prompt access to life-saving treatments, according to three-year data from the SMA screening program in the state of New York.
Gene therapy was the main treatment strategy, and delays in getting insurance were the main nonmedical reasons for lack or treatment delays. The results also confirmed earlier findings that the frequency of SMA in newborns may be lower than previously expected.
“Pre-symptomatic diagnosis and access to treatment has completely changed the course of the disease in these babies,” Bo Hoon Lee, MD, assistant professor of neurology at the University of Rochester Medical Center and the study’s first author, said in a press release. “To see children, who would have had severe weakness, walking and healthy is extremely rewarding.”
The report, “Newborn Screening for Spinal Muscular Atrophy in New York State: Clinical Outcomes From the First 3 Years,” was published in the journal Neurology.
In July 2018, SMA was added to the Recommended Uniform Screening Panel (RUSP) for newborns in the U.S., a list of conditions the U.S. Department of Health and Human Services recommends for state universal screening programs. Screening in New York state began four months later, in October.
Newborn screening uses a small blood sample collected shortly after birth to look for mutations that cause diseases like SMA. The screening is now available to 87% of all babies born in the United States.
The majority of SMA cases (95%) are caused by mutations in the SMN1 gene, which affects the production of SMN, a protein essential for muscle health. The existence of a second SMN gene, called SMN2, can compensate — in part — for the loss of SMN1-produced SMN. Typically, the more SMN2 gene copies a person has, the less severe the disease.
The screening allows for early SMA detection, which means that babies can get access to prompt treatment, increasing the likelihood of better future outcomes and before irreparable damage is done.
34 of nearly 650,000 test positive
Now, a team led by researchers at the Department of Neurology, University of Rochester, New York, released the findings from the first three years of screening.
In the three years since its implementation, nearly 650,000 infants in the state of New York have been screened for SMA. A total of 34 tested positive for the disease, which according to the researchers, reflects a lower incidence than previously predicted. Findings from a previous one-year report of the New York SMA screening program hinted at the same trend.
All infants were referred to a neuromuscular specialty care center, with 94% of them having had treatment. The gene therapy Zolgensma (onasemnogene abeparvovec-xioi), which delivers a functional version of the SMN1 gene to cells, was used in 97% of cases. This gene therapy uses a modified and harmless adeno-associated virus type 9 (AAV9) to deliver the working copy of the faulty gene.
According to clinical follow-up data from infants with three copies of SMN2, all were symptom-free after treatment. Those with two copies had more variable outcomes.
Data from an electrical study of muscle function, using a test called compound muscle action potential (CMAP), conducted before and after gene therapy were available for a group of 11 infants. CMAP results from the last follow-up showed motor function had either improved or stabilized after treatment.
The majority of infants were treated before reaching six weeks or 42 days (median 34.5 days).
“Even days or a week can make a difference,” said Basil T. Darras, MD, a professor of neurology at Harvard Medical School. “You can go from having a baby who has a totally normal physical exam at 10 days old to a baby who has low muscle tone, weakness, and loss of reflexes a week later. Time is motor neurons. You must intervene urgently. It’s a medical emergency.”
The presence of antibodies against AAV9 — a natural response from the immune system that can impair gene therapy’s efficacy — and elevated levels of troponin I protein, indicative of heart damage, were the main medical reasons for no treatment or for its delay. Nonmedical constraints included delays in obtaining insurance or insurance policies regarding specific treatments.
Overall, “the findings from the [New York state] cohort of newborn screen-identified infants are consistent with other reports of improved outcomes from early diagnosis and treatment,” the researchers wrote.
“Additional biomarkers of motor neuron health including electromyography [a diagnostic procedure to assess the health of muscles and the nerve cells that control them] can potentially be helpful in detecting pre-clinical decline,” they concluded.
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