Bram De Wel1,2, Veerle Goosens3, Atka Sobota4, Elke Van Camp4, Ellen Geukens5, Griet Van Kerschaver5, Marlène Jagut6, Kathleen Claes7,8, Kristl G Claeys9,10. 1. Department of Neurology, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. 2. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium. 3. Department of Radiology, University Hospitals Leuven, Leuven, Belgium. 4. Department of Physical and Rehabilitation Medicine (Physiotherapy), University Hospitals Leuven, Leuven, Belgium. 5. Department of Physical and Rehabilitation Medicine (Occupational Therapy), University Hospitals Leuven, Leuven, Belgium. 6. Belgian Neuromuscular Diseases Registry, Sciensano, Brussels, Belgium. 7. Department of Nephrology, University Hospitals Leuven, Leuven, Belgium. 8. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium. 9. Department of Neurology, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. Kristl.Claeys@uzleuven.be. 10. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium. Kristl.Claeys@uzleuven.be.
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.
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.
Authors: Eugenio Mercuri; Charlotte J Sumner; Francesco Muntoni; Basil T Darras; Richard S Finkel Journal: Nat Rev Dis Primers Date: 2022-08-04 Impact factor: 65.038
Authors: W David Arnold; Steven Severyn; Songzhu Zhao; David Kline; Matthew Linsenmayer; Kristina Kelly; Marco Tellez; Amy Bartlett; Sarah Heintzman; Jerry Reynolds; Gary Sterling; Tristan Weaver; Kiran Rajneesh; Arthur H M Burghes; Stephen J Kolb; Bakri Elsheikh Journal: BMJ Neurol Open Date: 2021-08-12
Authors: Bakri Elsheikh; Steven Severyn; Songzhu Zhao; David Kline; Matthew Linsenmayer; Kristina Kelly; Marco Tellez; Amy Bartlett; Sarah Heintzman; Jerry Reynolds; Gary Sterling; Tristan Weaver; Kiran Rajneesh; Stephen J Kolb; W David Arnold Journal: Front Neurol Date: 2021-04-16 Impact factor: 4.003
Authors: Bakri Elsheikh; Steven Severyn; Songzhu Zhao; David Kline; Matthew Linsenmayer; Kristina Kelly; Marco Tellez; Amy Bartlett; Sarah Heintzman; Jerry Reynolds; Gary Sterling; Tristan Weaver; Kiran Rajneesh; Stephen J Kolb; W David Arnold Journal: Front Neurol Date: 2021-05-20 Impact factor: 4.003
Authors: Maren Freigang; Claudia D Wurster; Tim Hagenacker; Benjamin Stolte; Markus Weiler; Christoph Kamm; Olivia Schreiber-Katz; Alma Osmanovic; Susanne Petri; Alexander Kowski; Thomas Meyer; Jan C Koch; Isabell Cordts; Marcus Deschauer; Paul Lingor; Elisa Aust; Daniel Petzold; Albert C Ludolph; Björn Falkenburger; Andreas Hermann; René Günther Journal: Ann Clin Transl Neurol Date: 2021-03-31 Impact factor: 4.511