Annals of Clinical and Translational Neurology (Aug 2021)
Nusinersen in pediatric and adult patients with type III spinal muscular atrophy
- Maria Carmela Pera,
- Giorgia Coratti,
- Francesca Bovis,
- Marika Pane,
- Amy Pasternak,
- Jacqueline Montes,
- Valeria A. Sansone,
- Sally Dunaway Young,
- Tina Duong,
- Sonia Messina,
- Irene Mizzoni,
- Adele D’Amico,
- Matthew Civitello,
- Allan M. Glanzman,
- Claudio Bruno,
- Francesca Salmin,
- Simone Morando,
- Roberto De Sanctis,
- Maria Sframeli,
- Laura Antonaci,
- Anna Lia Frongia,
- Annemarie Rohwer,
- Mariacristina Scoto,
- Darryl C. De Vivo,
- Basil T. Darras,
- John Day,
- William Martens,
- Katia A. Patanella,
- Enrico Bertini,
- Francesco Muntoni,
- Richard Finkel,
- Eugenio Mercuri,
- the iSMAC group
Affiliations
- Maria Carmela Pera
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- Giorgia Coratti
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- Francesca Bovis
- Biostatistics Unit Department of Health Sciences University of Genoa Genoa Italy
- Marika Pane
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- Amy Pasternak
- Department of Neurology Boston Children's Hospital Harvard Medical School Boston MassachusettsUSA
- Jacqueline Montes
- Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York New YorkUSA
- Valeria A. Sansone
- Neurorehabilitation Unit University of Milan Neuromuscular Omnicentre Clinical Center Niguarda Hospital Milan Italy
- Sally Dunaway Young
- Department of Neurology Stanford University Palo Alto CaliforniaUSA
- Tina Duong
- Department of Neurology Stanford University Palo Alto CaliforniaUSA
- Sonia Messina
- Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud University of Messina Messina Italy
- Irene Mizzoni
- Unit of Neuromuscular and Neurodegenerative Disorders Department of Neurosciences IRCCS Bambino Gesù Children's Hospital Rome Italy
- Adele D’Amico
- Unit of Neuromuscular and Neurodegenerative Disorders Department of Neurosciences IRCCS Bambino Gesù Children's Hospital Rome Italy
- Matthew Civitello
- Nemours Children’s Hospital University of Central Florida College of Medicine OrlandoUSA
- Allan M. Glanzman
- Department of Physical Therapy The Children's Hospital of Philadelphia Philadelphia PennsylvaniaUSA
- Claudio Bruno
- Center of Experimental and Translational Myology IRCCS Istituto Giannina Gaslini Genoa Italy
- Francesca Salmin
- Neurorehabilitation Unit University of Milan Neuromuscular Omnicentre Clinical Center Niguarda Hospital Milan Italy
- Simone Morando
- Center of Experimental and Translational Myology IRCCS Istituto Giannina Gaslini Genoa Italy
- Roberto De Sanctis
- Centro Clinico Nemo Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy
- Maria Sframeli
- Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud University of Messina Messina Italy
- Laura Antonaci
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- Anna Lia Frongia
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- Annemarie Rohwer
- Dubowitz Neuromuscular Centre UCL Institute of Child Health & Great Ormond Street Hospital London United Kingdom
- Mariacristina Scoto
- Dubowitz Neuromuscular Centre UCL Institute of Child Health & Great Ormond Street Hospital London United Kingdom
- Darryl C. De Vivo
- Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York New YorkUSA
- Basil T. Darras
- Department of Neurology Boston Children's Hospital Harvard Medical School Boston MassachusettsUSA
- John Day
- Department of Neurology Stanford University Palo Alto CaliforniaUSA
- William Martens
- University of Rochester Medical Center Rochester New YorkUSA
- Katia A. Patanella
- Department of Neurosciences Institute of Neurology Catholic University Rome Italy
- Enrico Bertini
- Unit of Neuromuscular and Neurodegenerative Disorders Department of Neurosciences IRCCS Bambino Gesù Children's Hospital Rome Italy
- Francesco Muntoni
- Dubowitz Neuromuscular Centre UCL Institute of Child Health & Great Ormond Street Hospital London United Kingdom
- Richard Finkel
- Nemours Children’s Hospital University of Central Florida College of Medicine OrlandoUSA
- Eugenio Mercuri
- Pediatric Neurology Università Cattolica del Sacro Cuore Rome Italy
- the iSMAC group
- DOI
- https://doi.org/10.1002/acn3.51411
- Journal volume & issue
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Vol. 8,
no. 8
pp. 1622 – 1634
Abstract
Abstract Objective We report longitudinal data from 144 type III SMA pediatric and adult patients treated with nusinersen as part of an international effort. Methods Patients were assessed using Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and 6‐Minute Walk Test (6MWT) with a mean follow‐up of 1.83 years after nusinersen treatment. Results Over 75% of the 144 patients had a 12‐month follow‐up. There was an increase in the mean scores from baseline to 12 months on both HFMSE (1.18 points, p = 0.004) and RULM scores (0.58 points, p = 0.014) but not on the 6MWT (mean difference = 6.65 m, p = 0.33). When the 12‐month HFMSE changes in the treated cohort were compared to an external cohort of untreated patients, in all untreated patients older than 7 years, the mean changes were always negative, while always positive in the treated ones. To reduce a selection bias, we also used a multivariable analysis. On the HFMSE scale, age, gender, baseline value, and functional status contributed significantly to the changes, while the number of SMN2 copies did not contribute. The effect of these variables was less obvious on the RULM and 6MWT. Interpretation Our results expand the available data on the effect of Nusinersen on type III patients, so far mostly limited to data from adult type III patients.
