Serum Troponin T levels as a therapy response marker in SOD1-mediated ALS

AbstractIntroductionSerum cardiac troponin T (cTnT) levels are elevated in the majority of amyotrophic lateral sclerosis (ALS) patients and increase over time. Neurofilament light chain (NfL) is an established therapy response biomarker in ALS as superoxide dismutase 1 (SOD1)-ALS patients treated with the antisense oligonucleotide tofersen show a decrease in NfL. In this study we assess the course of cTnT levels in SOD1-ALS at baseline and during tofersen treatment.MethodsSerum cTnT was analyzed at baseline and during tofersen treatment in 23 SOD1-ALS patients at two specialized ALS centers in Germany and compared to a control cohort of 74 ALS patients without SOD1-mutations and not treated with tofersen.ResultscTnT levels increased in the control ALS-cohort over time (p<0.0001) but not in the tofersen group (p=0.36). CK, and CK-MB levels did not show relevant changes over time. The median monthly increase of cTnT was 0.045 points (IQR 0.02-0.08) in the control ALS cohort and 0.01 points (IQR −0.01-0.03) in the tofersen group (p=0.0013). The fold change in cTnT levels of the tofersen-treated cohort (median 1.2; IQR 0.77-1.59) was significantly less and even showed a reduction in some patients compared to the control group (median 1.89; IQR 1.35-2.75) (p=0.0003).DiscussionIn this study, we find a response signal of cTnT to tofersen treatment, which supports the value of cTnT as an independent biomarker in ALS. These results contribute to the notion that cTnT may provide additional value as a progression and treatment response biomarker in ALS complementary to NfL and warrant further investigations.Graphical Abstract