Tofersen treatment in respiratory onset amyotrophic lateral sclerosis and a variant of uncertain significance in SOD1; a case report.
Sean W Willemse, Koen C Demaegd, Wouter Koole et al.
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Case in brief
A patient with respiratory onset amyotrophic lateral sclerosis (ALS) and a novel SOD1 variant of uncertain significance (VUS) was treated with tofersen. After six months, significant reductions in cerebrospinal fluid SOD1 protein (47%) and neurofilament light chain (NfL) levels (55% in CSF and 50% in serum) were observed. Functional decline slowed markedly, and muscle strength and quality of life remained stable.
Diagnostic / clinical pearl
This case highlights the potential for treatment response in ALS patients with SOD1 variants of uncertain significance, suggesting that such variants may be viable targets for gene-specific therapies.
Why it matters
As gene-targeted treatments for ALS evolve, understanding the clinical implications of variants of uncertain significance will be crucial for personalized patient management.