Blood biomarker ratio may track Spinraza response in SMA children
The blood creatinine-to-cystatin-c ratio (CCR), an indicator of muscle mass and strength, may be a biomarker of treatment response in children with spinal muscular atrophy (SMA), a study in China shows.
Increases in the ratio were significantly associated with gains in motor function following long-term treatment with Spinraza (nusinersen).
Although larger studies are needed to validate these findings, the study’s researchers “propose that CCR should be routinely monitored in the longitudinal follow-up of all patients with SMA,” as it is a “simple, inexpensive, and accessible measurement.”
The study, “Serum creatinine to cystatin C ratio as a biomarker for monitoring motor-function in children with spinal muscular atrophy treated with nusinersen: a retrospective cohort study,” was published in BMC Neurology.
Spinraza targets key backup gene
SMA is chiefly caused by mutations in the SMN1 gene that result in a deficiency of the SMN protein, which is essential for muscle health. The lack of this protein leads to the loss of motor neurons — the nerve cells that control movement — and to SMA symptoms, such as muscle weakness and wasting.
Spinraza, a widely approved SMA therapy that increases SMN levels by acting on a backup gene called SMN2, has led to stable or improved motor function, especially when given before symptoms arise.
Tools used in clinical practice have provided valuable information, but they are time-consuming and require expertise, so “there is a need for reliable biomarkers to complement the clinical evaluation,” the scientists wrote.
The CCR ratio, calculated by dividing the level of creatinine by that of cystatin C (CysC), has been developed as a marker of muscle mass and has shown correlations with muscle volume and functional performance. Low creatinine has been associated with increased disease severity in SMA patients, while CysC is a known indicator of kidney function.
Ratio higher for children with four SMN2 copies
In this study, researchers in China evaluated the link between these blood biomarkers and treatment response in 33 Chinese children with SMA receiving Spinraza. Their median age at genetic diagnosis was 18 months (about 1.5 years), and most were girls (57.6%).
Nineteen children had SMA type 2, while 11 had SMA type 3, two had SMA type 1, and one still had no symptoms. The majority could not walk before starting Spinraza. A 17-year-old was able to walk after starting the treatment, and a child who began on Spinraza at 40 days of age, before SMA symptoms appeared, achieved age-appropriate motor milestones.
Functional and motor assessments, along with blood biomarker measurements, were conducted at the study’s start and for up to 26 months (more than two years). The number of SMN2 gene copies was also assessed: 25 participants had three copies, and six had four. More copies are typically associated with less severe disease.
Children with four SMN2 copies had significantly higher CCR — 23.8 vs. 9.1 micromoles (mcmol)/mg — and creatinine levels (20 vs. 8 mcmol/L) than those with three gene copies. Similar differences were observed between children who could walk and those who couldn’t.
CCR is a potential prognostic biomarker in paediatric patients with SMA receiving [Spinraza] monotherapy.
In follow-up measurements, CCR progressively increased, with that elevation detectable from 10 months of treatment. Creatinine exhibited a more gradual increase, becoming significant after a little more than two years. In contrast, blood creatine kinase, a marker of muscle damage, and CysC levels remained stable during the study period.
After adjusting for age at Spinraza initiation, treatment duration, body mass index (a measure of body fat based on weight and height), and SMA type, CCR was associated with greater improvements in motor function, as assessed by the Hammersmith Functional Motor Scale-Expanded, and arm and hand performance, measured by the Revised Upper Limb Module.
Additionally, children with higher CysC levels had lower Hammersmith Infant Neurological Exam-Part 2 scores, a test that helps determine whether children are able to reach motor milestones.
“Our observation of an inverse correlation between CysC levels and motor function scores in SMA aligns with this emerging concept of CysC as a potential biomarker associated with neural dysfunction,” the scientists wrote. “Although SMA primarily affects motor neurons, the elevated CysC levels observed in our patients may indicate the presence of secondary neurodegenerative processes or potentially compromised renal clearance [function].
They concluded that “CCR is a potential prognostic biomarker in paediatric patients with SMA receiving [Spinraza] monotherapy.”
The post Blood biomarker ratio may track Spinraza response in SMA children appeared first on SMA News Today.
