scholarly journals Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I

2021 ◽  
Vol 10 (23) ◽  
pp. 5540
Author(s):  
Andrada Mirea ◽  
Elena-Silvia Shelby ◽  
Mihaela Axente ◽  
Mihaela Badina ◽  
Liliana Padure ◽  
...  

Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.

Neurology ◽  
2018 ◽  
Vol 91 (14) ◽  
pp. e1312-e1318 ◽  
Author(s):  
Karolina Aragon-Gawinska ◽  
Andreea M. Seferian ◽  
Aurore Daron ◽  
Elena Gargaun ◽  
Carole Vuillerot ◽  
...  

ObjectiveTo evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1).MethodsPatients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32).ResultsWe treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment (p < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 (SMN2) gene.ConclusionsOur results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease.ClinicalTrials.gov identifier:NCT02865109.Classification of evidenceThis study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.


2021 ◽  
Vol 40 (4) ◽  
pp. 1578-1587
Author(s):  
Andrea Foppiani ◽  
Ramona De Amicis ◽  
Alessandro Leone ◽  
Simone Ravella ◽  
Giorgio Bedogni ◽  
...  

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1039
Author(s):  
Minsu Gu ◽  
Hyun-Ho Kong

Although nusinersen has been demonstrated to improve motor function in patients with spinal muscular atrophy (SMA), no studies have investigated its effect on fine manual dexterity. The present study aimed to investigate the ability of nusinersen to improve fine manual dexterity in patients with SMA type 2. A total of five patients with SMA type 2 were included. The Hammersmith Functional Motor Scale (expanded version) (HFMSE) and Purdue Pegboard (PP) tests were used to evaluate gross motor function and fine manual dexterity, respectively, until 18 months after nusinersen administration. HFMSE scores improved by 3–10 points (+13–53%) in all patients following nusinersen administration. PP scores also improved in all patients, from 4 to 9 points (+80–225%) in the preferred hand and from 3 to 7 points (+60–500%) in the non-preferred hand. These results suggest that nusinersen treatment improved both gross motor function and fine manual dexterity in children with SMA type 2. Addition of the PP test may aid in evaluating the fine manual dexterity essential for activities of daily living in these patients.


2019 ◽  
Vol 36 (5) ◽  
pp. 1164-1176 ◽  
Author(s):  
Omar Dabbous ◽  
Benit Maru ◽  
Jeroen P. Jansen ◽  
Maria Lorenzi ◽  
Martin Cloutier ◽  
...  

Author(s):  
Renske I Wadman ◽  
W Ludo van der Pol ◽  
Wendy MJ Bosboom ◽  
Fay-Lynn Asselman ◽  
Leonard H van den Berg ◽  
...  

2008 ◽  
Vol 18 ◽  
pp. S43-S47 ◽  
Author(s):  
Adele D'Amico ◽  
Marina Cuttini ◽  
Lucilla Ravà ◽  
Eugenio Mercuri ◽  
Sonia Messina ◽  
...  

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