Affiliations: [a] Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany
Medical Genetics Center – MGZ, Munich, Germany
Correspondence to: Maggie C. Walter, MD, MA Friedrich-Baur-Institute Department of Neurology, Ludwig-Maximilians-University of Munich, Ziemssenstrasse 1, 80336 Munich, Germany. Tel.: +49 89 4400 57400; Fax: +49 89 4400 57402; E-mail: [email protected].
Abstract: Background:Spinal muscular atrophy is an autosomal recessive neuromuscular disease leading to ongoing degeneration of anterior horn cells in the spinal cord. Nusinersen is the first approved treatment for the condition, an intrathecally administered antisense oligonucleotide. It modulates pre-RNA splicing of the SMN2 gene and increases full-length SMN protein expression, thereby increasing SMN protein levels. The benefit of Nusinersen for patients with spinal muscular atrophy type 3 (SMA3) has recently been shown in several real-world cohorts. Objective:We aim to elucidate not only the effect of therapy with Nusinersen, but the development of the disease course after discontinuation of treatment. To our knowledge, there are so far no reports on the effects of Nusinersen discontinuation. Methods:We report on a 45-year-old female patient with genetically confirmed SMA3 and a disease duration of 40 years prior to treatment onset. Results:The patient was non-ambulantory, best motor function at treatment onset was holding arms with support, reflected in MRC of 3/5 in upper limbs. After having received Nusinersen for 11 months without complications, the patient showed improvement in motor functions, as measured by hand grip measurement (HGS), Hammersmith Functional Rating Scale Expanded (HFMSE), and Revised Upper Limb Module (RULM). Due to worsening of a pre-existing anxiety disorder, treatment was discontinued after six injections. Sixteen months later, progression of the disease became evident with worsening of HFMSE and RULM scores, while hand strength remained stable. Conclusion:Treatment with Nusinersen in SMA3 improves motor function in longstanding disease even in clinically advanced stages; however, after discontinuation of treatment, further progression mirroring the natural history of the disease is anticipated.
Keywords: Spinal muscular atrophy type 3, SMA3, nusinersen, hammersmith functional motor scale, revised upper limb module, outcome measure