An observational study of functional abilities in infants, children, and adults with type 1 SMA

Pane, Marika; Palermo, Concetta; Messina, Sonia; Sansone, Valeria; Bruno, Claudio; Catteruccia, Michela; Sframeli, Maria; Albamonte, Emilio; Pedemonte, Marina; D’Amico, Adele; Brigati, Giorgia; Sanctis, Roberto De; Coratti, Giorgia; Lucibello, Simona; Bertini, Enrico; Vita, Giuseppe; Tiziano, Francesco Danilo

doi:10.1212/wnl.0000000000006050

Cited by 32 publications

(38 citation statements)

References 22 publications

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“…A recent natural history study reported that only 50% of untreated infants with SMA1 with two copies of SMN2 reached a median age of eight months free of permanent ventilation. 4 In contrast to natural history, in which no patient achieved a CHOP-INTEND score above 40, 15 11 of 12 patients in this study achieved and maintained a CHOP-INTEND score of 40. Patients in the Early Dosing/Low Motor group had rapid mean increases in CHOP-INTEND of 13.7 and 22.0 points at one and three months, respectively.…”

Section: Discussioncontrasting

confidence: 70%

“…14 Efficacy in motor function is further validated when compared with the poor outcomes associated with severe variants of SMA1 (mean CHOP-INTEND scores of 4.1 to 5.4 and death by age 14 months). 15 These results show the efficacy of using AVXS-101 and support identifying infants via newborn screening to maximize the therapeutic benefit of early treatment, as recently recommended by a panel of SMA experts. 17 The findings also indicate that gene transfer with AVXS-101 is highly relevant and effective for patients with early onset and low CHOP-INTEND scores.…”

Section: Discussionsupporting

confidence: 59%

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Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy

Lowes

Alfano

Arnold

et al. 2019

Pediatric Neurology

152

123

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Background: This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1). Methods: This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores <20 (n ¼ 3), (2) late dosing, dosed at age three months or greater (n ¼ 6), and (3) early dosing/high motor, dosed age less than three months with scores 20 (n ¼ 3). Results: Early dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months). Conclusions: The rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionsupporting

confidence: 59%

Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy

Lowes

Alfano

Arnold

et al. 2019

Pediatric Neurology

152

123

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“…In our study the SATR test revealed that chest deformities in SMA patients occurred more often and were significantly severe than in the healthy individuals. The highest values of SATR were noted in individuals with SMA I and SMA II who most often experienced breathing difficulties and need non-invasive ventilatory support [ 32 – 34 ]. In the case of patients with SMA III, the test revealed significantly lower values of chest deformities compared to SMA I and SMA II participants.…”

Section: Discussionmentioning

confidence: 99%

Cervical rotation, chest deformity and pelvic obliquity in patients with spinal muscular atrophy

Stępień

Mazurkiewicz

Maślanko³

et al. 2020

BMC Musculoskelet Disord

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Background Musculoskeletal disorders are often observed in patients with spinal muscular atrophy (SMA). The aim of the study was to assess passive ranges of rotation in the cervical spine, chest deformity and pelvic obliquity in SMA patients, and to compare these results to the norms obtained in the group of healthy individuals. The second aim was to review these measurements and Cobb angle values for correlations in SMA patients. Methods The study included 74 patients with SMA and 89 healthy individuals aged 2 to 18 years. Cervical Rotation (CR), Supine Angle of Trunk Rotation (SATR) and Pelvic Obliquity (PO) tests were carried out. Results Cervical rotation ranges were significantly higher in the control group than in SMA patients (p < 0.05). Differences between cervical rotation ranges to the left and to the right were significantly larger in SMA I and SMA II groups than in healthy individuals (p = 0.000). Chest asymmetry and pelvic obliquity were bigger in SMA groups than in the control (p < 0.05). Significant correlations between cervical rotation measurements, chest deformity, pelvic obliquity and Cobb angle were found in SMA individuals, depending on the type. Conclusions The results of the study suggest that CR, SATR and PO tests may assist in the assessment of SMA patients in addition to the radiographic evaluation of the spine. Biomechanical relationships between disorders located in various skeletal structures should be taken into account in the treatment of SMA patients. Special attention should be given to assessing postural parameters in non- sitters and sitters. Treatment of patients with SMA and associated musculoskeletal disorders requires a multi-specialist approach.

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“…It is an autosomal recessive neuromuscular disease (NMD) caused by a homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene on chromosome 5q13, characterized by progressive muscle wasting and debilitating weakness [3][4][5][6][7]. The disease has been classified into subtypes based upon age of onset and motor function achieved [4,[8][9][10]. Type I has onset in infancy and is the most severe and common subtype (representing 50-60% of diagnoses), whereas types II, III, and IV represent later onset, milder phenotypes [4,[9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…The disease has been classified into subtypes based upon age of onset and motor function achieved [4,[8][9][10]. Type I has onset in infancy and is the most severe and common subtype (representing 50-60% of diagnoses), whereas types II, III, and IV represent later onset, milder phenotypes [4,[9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The SMA Clinical Trial Readiness Program: creation and evaluation of a program to enhance SMA trial readiness in the United States

Peterson¹,

Cruz

Sarr³

et al. 2020

Orphanet J Rare Dis

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Spinal muscular atrophy (SMA) is a rare neuromuscular disease with a rapidly evolving treatment landscape. To better meet the needs of trial sponsors and the patient community in the United States (US) in this evolving context, Cure SMA established a clinical trial readiness program for new and prospective SMA clinical trial sites. Program development was informed by a review of the SMA clinical trial landscape, successful NMD trial and care networks, and factors important to effective trial conduct in SMA. The program was piloted in 2018 with a virtual site readiness evaluation, a trial readiness toolkit, and a readiness program for physical therapists and clinical evaluators. Nine US research hospitals participated in the pilot. Cure SMA evaluated the pilot program and resources through feedback surveys, which supported the program’s relevance and value. Since 2018, the program has been expanded with additional sites, new best practices toolkits, and workshops. In partnership with Cure SMA, SMA Europe is also extending programming to European countries. The program is significant as an example of a patient advocacy group working successfully with pharmaceutical companies, other patient advocacy organizations, and research hospitals to promote trial readiness, and may serve as a model for organizations in other regions and diseases.

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An observational study of functional abilities in infants, children, and adults with type 1 SMA

Cited by 32 publications

References 22 publications

Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy

Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy

Cervical rotation, chest deformity and pelvic obliquity in patients with spinal muscular atrophy

The SMA Clinical Trial Readiness Program: creation and evaluation of a program to enhance SMA trial readiness in the United States

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