Noninvasive quantification of fasciculations to track tofersen therapy in SOD1-ALS: the first case series

<h3></h3> Tofersen (Qalsody, Biogen) is an intrathecally administered antisense oligonucleotide that inhibits mutant superoxide dismutase-1 (SOD1) protein synthesis in 2% of patients with amyotrophic lateral sclerosis (ALS). This novel therapy has been made available to ALS-SOD1 patients in the UK through the Biogen Early Access Programme. For the first time, this case series evaluates the quantification of fasciculations in SOD1-ALS patients receiving tofersen treatment. Six patients underwent high-density surface electromyography involving three muscles (biceps brachii, first dorsal interosseus, and tibialis anterior) on the day of fortnightly or monthly tofersen treatment. Muscles were individually categorised as either ‘strong’ (5/5 power at each visit) or ‘weak’. Fasciculation frequency and amplitude were quantified using the Surface Potential Quantification Engine. Results from 66 recordings indicated a pattern of fasciculation behaviour that contrasted with ALS natural history data. In weak biceps brachii muscles, fasciculation frequency appeared to be maintained with a reduced fasciculation amplitude over time, suggesting relative maintenance of the motor unit pool and reduced need for compensatory reinnervation. These findings underscore the utility of high-density surface electromyography in this context, emphasising the importance of a larger study with more intensive monitoring between doses to better understand the relationship between fasciculation behaviour and tofersen therapy.