A natural history comparison of SOD1 -mutant patients with amyotrophic lateral sclerosis between Chinese and German populations

Currently,there is no effective treatment for amyotrophic lateral sclerosis (ALS),despite the limited efficacy of rilu-zole [1] and edaravone [2].SOD1 (coding for the Cu/Zn superoxide dismutase) is the second most frequent genetic cause for ALS only after C9orf72 in patients with European ancestry while being the most frequent in Asian ALS populations [3].Multiple therapeutic approaches have targeted SOD1-related ALS,including the antisense oligonucleotide tofersen with promising results in a recent phase Ⅰ/Ⅱ trial [4].Given the clinical heterogeneity among different SOD1 mutations,in this study,we enrolled genetically confirmed ALS patients with SOD1 mutations from two prospectively established hospital-based cohorts from China [5] and Germany [6]to clinically characterize distinct SOD1 mutations and compare related phenotypes between Asians and Cau-casians.Because of the explorative nature of this study,all results should be interpreted as hypothesis-generating only rather than confirmatory.No adjustment for multi-ple testing was made.