Heart marker troponin-I best tested in each SMA newborn: Study
Blood levels should be measured before and after gene therapy in infants
Blood levels of troponin-I, a marker for heart muscle damage, are best measured before and after gene therapy in each newborn with spinal muscular atrophy (SMA), a new study concluded.
Although elevated troponin-I has been associated with SMA gene therapy, levels above the reference values generated from adults were found in newborns with and without SMA.
As such, “post-treatment elevations should be interpreted in the context of the course rather than as individual values,” the researchers wrote.
The study, “High-sensitive cardiac troponin I (hs-cTnI) concentrations in newborns diagnosed with spinal muscular atrophy,” was published in the journal Frontiers in Pediatrics.
Blood test data on troponin-I collected from 30 newborns
SMA is caused by mutations in the SMN1 gene, which leads to a deficiency in the SMN protein. The absence of SMN activity mainly affects motor neurons, the cells in the brain and spinal cord that facilitate movement, speech, breathing, and swallowing.
Zolgensma (onasemnogene abeparvovec-xioi) is the only one-time gene therapy approved in the U.S. to treat newborns and toddlers up to age 2 with all SMA types. It works by delivering a working copy of SMN1 to the body’s cells with the goal of increasing SMN protein levels.
In clinical trials and post-marketing studies, Zolgensma treatment was associated with elevated levels of troponin-I, a biomarker indicating potential damage to heart muscles.
According to researchers in Germany, however, pre-therapeutic and age-appropriate reference values for this biomarker in newborns with SMA are lacking. They argue that such values are “relevant for the decision making” when administering gene therapies like Zolgensma.
To address this gap, blood test data were collected from 30 newborns — 19 girls and 11 boys — with genetically confirmed SMA. The data was collected before treatment with at least one troponin-I value in the first 28 days of life. Troponin-I levels also were measured in 16 newborns without SMA or heart disease.
“This is the first report of [troponin-I] levels in newborns with genetically confirmed [SMA],” the researchers noted.
Four patients showed heart abnormalities on echocardiograms and three by electrocardiogram (ECG). SMA symptoms — including low muscle tone, reduced head control or spontaneous movements, a lack of reflexes, and/or uncontrolled tongue movements — were observed in five SMA newborns.
Six neuromuscular centers provided troponin-I values, each using a different commercial high-sensitivity testing method. Test-specific upper reference levels, generated from adults, ranged from 15.6 to 45 nanograms per liter of blood (ng/L).
Data showed that 16 of the 30 untreated SMA newborns — a total of 53% — had a troponin-I value above the test-specific upper reference levels in blood plasma, the liquid portion of blood without cells.
The researchers noted that the wide variation in troponin-I concentrations, which ranged from 4 to 1205 ng/L, was due to high values in one patient. While this patient was born without complications and had no SMA symptoms, echocardiograms revealed a congenital heart defect. An elevated level of NT-proBNP, a marker for heart injury, also was noted in this patient.
Based on echocardiograms or ECGs, cardiac abnormalities were seen in patients with troponin-I values below the test-specific upper reference levels. Only one of the newborns with SMA symptoms had troponin-I levels slightly above the reference level.
Pre-therapeutic measurement of [troponin-I] is especially important for the interpretation of the course of post-treatment [troponin-I] values.
Statistical analysis revealed no relevant relationships between troponin-I values and various clinical factors. These included newborn age, gestational age, mode of birth delivery, SMA symptoms, motor function, NT-proBNP levels, or abnormal cardiac findings.
Among 10 of the 15 patients with a troponin-I value taken after the newborn period, five saw their levels drop from above to below the upper reference range during follow-up, whereas five remained above.
In comparison, of the 16 newborns without SMA or heart disease tested, nine had troponin-I levels within the normal range, and seven (44%) had concentrations above the test-specific upper reference limit.
“Our results suggest higher [troponin-I] plasma levels in newborns with and without SMA compared to assay-specific reference values generated in adults,” the researchers wrote. Because of the large age-related distribution of values, “pre-therapeutic measurement of [troponin-I] is especially important for the interpretation of the course of post-treatment [troponin-I] values.”
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