Abstract
Background Nusinersen recently became available as the first treatment for Spinal Muscular Atrophy (SMA) and data on
its effectiveness and safety in adult SMA patients are still scarce.
Methods We evaluated the effectiveness and safety of nusinersen treatment during 14 months in 16 adult patients with SMA
types 3 and 4 in a prospective study, and retrospectively detailed the natural history of 48 adult SMA patients types 2, 3 and 4.
Results Hand grip strength (p = 0.03), hand motor function (p = 0.04) as assessed by a sub-score of the Revised Upper
Limb Module (RULM) and the Medical Research Council (MRC) sum score (p = 0.04) improved significantly at month 14.
Importantly, the MRC sum score had declined significantly (p < 0.01) prior to start of treatment in these patients. A minimal
clinically important difference (MCID) in the Hammersmith Functional Motor Scale Expanded (HFMSE) and RULM scores
was achieved in 31% and 50% of the patients, respectively, but the mean changes from baseline failed to reach significance.
Forced Vital Capacity (FVC) transiently increased at month 6 (p = 0.01), whereas the Peak Expiratory Flow (PEF) did not.
The Activity Limitations scale declined significantly prior to start of treatment (p < 0.01) and showed an improvement with
nusinersen which was not significant. The safety evaluation did not reveal serious adverse events and no signs of nephrotoxicity
or antisense oligonucleotide (ASO)-mediated inflammation.
Conclusions We conclude that hand grip strength and hand motor function, as well as MRC sum scores improved significantly
in nusinersen-treated adult patients with SMA types 3 and 4.
