Longitudinal Assessment of Timed Function Tests in Ambulatory Individuals with SMA Treated with Nusinersen

Article type: Research Article

Authors: Krosschell, Kristin J.^{a; b; *} | Brown, Laurey^{c; d} | Hoffman, Katie^{c; d} | Zumpf, Katelyn B.^{e; f} | Munson, Hannah^g | Bidwell, Jessa^h | Schulte, Duncan P.^d | Schwaede, Abigail N.^{b; d} | Buehner, Amber N.ⁱ | DiDonato, Christine J.^{b; j} | Kuntz, Nancy L.^{b; d} | Rao, Vamshi K.^{b; d; j}

Affiliations: [a] Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, USA | [b] Department of Pediatrics, Northwestern University Feinberg School of Medicine, USA | [c] Department of Rehabilitation Services, Ann and Robert H. Lurie Children’s Hospital of Chicago, USA | [d] Division of Neurology, Ann and Robert H. Lurie Children’s Hospital of Chicago, USA | [e] Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA- sponsor | [f] Statistical Consulting, OSF Healthcare, Chicago, IL, USA | [g] Chicago College of Osteopathic Medicine, Midwestern University Downers Grove, IL, USA | [h] Graduate Program of Genetic Engineering, Northwestern University, Chicago, IL, USA | [i] Ultragenyx Pharmaceutical, Inc, USA | [j] Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago, USA

Correspondence: [*] Correspondence to: Kristin J. Krosschell, PT, DPT, MA, PCS, Department of Physical Therapy & Human Movement Sciences and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Tel.: +1 312 908 6790; Fax: +1 312 908 8160; E-mail: [email protected].

Abstract: Background:Ambulatory individuals with spinal muscular atrophy experience weakness and impairments of speed and endurance. This leads to decreased motor skill performance required for daily living including transitioning from floor to stand, climbing stairs, and traversing short and community distances. Motor function improvements have been reported in individuals receiving nusinersen, but changes in timed functional tests (TFTs) which assess shorter distance walking and transitions have not been well documented. Objective:To evaluate changes in TFT performance over the course of nusinersen treatment in ambulatory individuals with SMA and identify potential factors [age, SMN2 copy number, BMI, Hammersmith Functional Motor Scale Expanded (HFMSE score), Peroneal Compound Motor Action Potential (CMAP) amplitude] associated with TFT performance. Methods:Nineteen ambulatory participants receiving nusinersen were followed from 2017 through 2019 (range: 0–900 days, mean 624.7 days, median 780 days); thirteen of 19 (mean age = 11.5 years) completed TFTs. The 10-meter walk/run test, time-to-rise from supine, time-to-rise from sitting, 4-stair climb, 6-minute walk test (6MWT), Hammersmith Expanded and peroneal CMAP were assessed at each visit. Linear mixed-effects models were used to evaluate unadjusted and adjusted changes in these outcomes over time. Results:Apart from time to rise from sitting and from supine, all TFTs were found to improve over the course of treatment after adjusting for baseline age and BMI. Conclusions:Improvement in TFTs over time in patients with SMA treated with nusinersen suggests that shorter TFTs may have value to assess individuals with SMA who have or later gain ambulatory function during treatment.

Keywords: Spinal muscular atrophy (SMA), Nusinersen, 10-meter walk/run test (10MWRT), Timed function tests (TFT), 6-minute walk test (6MWT), Time to climb 4 stairs (TTC-4 stairs), Time to rise from supine (TTR-supine), Time to rise from bench (TTR-bench), Hammersmith Functional Motor Scale Expanded (HFMSE), Compound motor action potential (CMAP)

DOI: 10.3233/JND-221519

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 3, pp. 337-348, 2023