Measuring Outcomes in Adults with Spinal Muscular Atrophy – Challenges and Future Directions – Meeting Report

Article type: Meeting Report

Authors: Sansone, V.A.^{a; 1} | Walter, M.C.^{b; 1} | Attarian, S.^c | Delstanche, S.^d | Mercuri, E.^{e; f} | Lochmüller, H.^{g; h; i} | Neuwirth, C.^j | Vazquez-Costa, J.F.^{k; l; m; n} | Kleinschnitz, C.^o | Hagenacker, T.^{o; *}

Affiliations: [a] The NEMO Clinical Center, Milan - Neurorehabilitation Unit, University of Milan, Italy | [b] Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, Germany | [c] Reference Center for Neuromuscular Disorders and ALS, CHU La Timone, Aix-Marseille University, Marseille, France | [d] Department of Neurology, University of Liege, Belgium | [e] Department of Pediatrics, Catholic University of Rome, Roma, Italy | [f] Department of Woman and Child Health and Public Health, Paediatric Neurology and Neuromuscular Omnicentre Clinical Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma, Italy | [g] Department of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany | [h] Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada | [i] Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada | [j] Muskelzentrum ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland | [k] Instituto de Investigacion Sanitaria la Fe (IIS La Fe), Neuromuscular Research Unit, Valencia, Spain | [l] Department of Neurology, ALS Unit, Hospital Universitario y Politecnico La Fe, Valencia, Spain | [m] Centro de Investigacion Biomedica en Red de EnfermedadesRaras (CIBERER), Valencia, Spain | [n] Department of Medicine, University of Valencia, Valencia, Spain | [o] Department of Neurology, University of Essen, Essen, Germany

Correspondence: [*] Correspondence to: Tim Hagenacker, MD, Department of Neurology, University Hospital Essen, Germany. Tel.: +49 201 723 6513; Tim.hagenacker@uk-essen.de

Note: [1] Equal contribution.

Abstract: Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease which affects 1 in 6,000–10,000 live births, caused by loss of the survival motor neuron 1 gene (SMN1). A major focus of therapeutic developments has been on increasing the full-length SMN protein by increasing the inclusion of exon 7 in SMN2 transcripts, enhancing SMN2 gene expression, stabilizing the SMN protein or replacing the SMN1 gene. In June 2017, FDA and EMA have approved the antisense oligonucleotide Nusinersen as the first treatment for all SMA subtypes without age restriction. While prominent treatment effects have been observed in the earlier stages of the disease and in patients up to 15 years of age, there is only limited data from clinical trials in adult SMA patients. First real-world data from neuromuscular clinical centers suggest a therapeutic benefit of nusinersen with a favourable safety profile also in adult SMA patients: in several cases, relevant improvements of motor function is achieved, which might lead to enhanced autonomy in daily life activities and improved quality of life. Systematic follow-up of the motor status with validated instruments is crucial for an adequate monitoring of the therapeutic effects but most of the widely used scales and scores have been developed and evaluated for the pediatric population only. International neuromuscular experts have met in Frankfurt/Main, Germany in May 2019 to discuss relevant aspects of the diagnostic pathway and patient management in adult SMA. The recommendations and challenges in this patient population are discussed.

Keywords: 5q-SMA, adult SMA, spinal muscular atrophy, motor neuron, nusinersen

DOI: 10.3233/JND-200534

Journal: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 523-534, 2020