Troponin T protein elevated in SMA; might reflect muscle damage
Elevated levels in SMA may mean TNT is released from skeletal muscle cells
The troponin T (TNT) protein — a marker of heart muscle damage — was elevated in the bloodstream of more than half of spinal muscular atrophy (SMA) patients, especially in younger children with more severe disease, a recent analysis shows.
Another heart-specific form of troponin called troponin I (TNI) wasn’t elevated in patients, which supports the idea that TNT is released not just from the heart, but also from skeletal muscle cells and could be a marker of skeletal muscle damage, researchers said.
The biomarker was decreased in response to treatment with Spinraza (nusinersen) among some adults, but not as strongly as other muscle damage biomarkers.
For this reason, while TNT may be “limited” as a SMA biomarker, the findings support “the potential usefulness of fluid molecular skeletal muscle markers as biomarkers for SMA,” the researchers wrote in “Troponin T is elevated in a relevant proportion of patients with 5q-associated spinal muscular atrophy,” which was published in Scientific Reports.
Muscle weakness and wasting are hallmark symptoms of SMA, so identifying muscle health biomarkers for monitoring disease progression and treatment responses is of interest to researchers.
Troponin is in muscle cells of the heart, but normally has very low or undetectable levels in the bloodstream. If the heart muscle is damaged, however, troponin leaks into the blood, such that elevations of TNT and TNI in the blood are considered strong biomarkers of heart muscle damage due to a heart attack.
While TNI seems more specific to the heart, elevations in TNT have been observed in a number of other diseases, including those of the skeletal muscles. That suggests TNT might be released from muscles outside the heart, making it a possible biomarker for neuromuscular diseases.
Is TNT coming from skeletal muscles?
Here, scientists in Germany explored TNT’s role as a biomarker in SMA and measured disease-related changes in its levels among 45 children and 48 adults with the main types of SMA at hospitals in Germany.
Data were collected from the patients when they were still treatment-naïve, that is, before they received SMA therapies, and throughout up to 38 months, or more than three years, of treatment.
At the start of the analysis, or its baseline, no patients had elevations in TNI, while 61% had TNT elevations according to the cutoffs used to identify cardiac events. TNT levels were higher among those with SMA type 1, generally a more severe form of disease, than those with SMA type 2 or type 3.
Given that TNI didn’t show any elevations, but TNT did, the researchers believe the findings indicate the biomarker isn’t coming from the heart, but instead “originates from degenerating or regenerating skeletal muscle fibers in patients with SMA.”
Among adults, 33.3% had elevated TNT. Levels of the protein correlated with other markers of muscle damage and mass, further supporting the idea that the protein is coming from the skeletal muscles, the scientists said.
Men had higher TNT levels than women, but the scientists said they didn’t have a “conclusive explanation” for this difference.
TNT was elevated in 86.1% of the children, with average levels substantially higher than the adults’ averages. “TNT elevation was more than twice as prominent and three times higher in children compared to adults,” the researchers wrote.
Higher TNT levels in children were observed in younger patients and those with indicators of more severe disease, including a more severe SMA type and fewer copies of the SMN2 gene.
TNT levels decreased after around three years of Spinraza treatment (34 and 38 months) over the baseline among the adults with biomarker elevations at the baseline.
Still, changes in TNT with treatment “seems to be much weaker” than that with other markers of muscle integrity, meaning “the added biomarker value of TNT for monitoring therapeutic effects under disease-modifying therapies seems to be low,” the researchers said.
The results from adults on Evrysdi (risdiplam) and children on any SMA therapy were more limited, and there generally were not enough data points to draw significant conclusions, leading the researchers to suggest that “longer observations periods” could result in better conclusions on the dynamics of TNT in infants and children on disease-modifying treatment.
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