How does intrathecal injected nusinersen compare with sham procedure for infants with spinal muscular atrophy (SMA) type I?

AbstractIn this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

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The natural history of type I (severe) spinal muscular atrophy

Neuromuscular Disorders ◽

10.1016/0960-8966(94)90090-6 ◽

1994 ◽

Vol 4 (5-6) ◽

pp. 497-502 ◽

Cited By ~ 75

Author(s):

N.H. Thomas ◽

V. Dubowitz

Keyword(s):

Natural History ◽

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Type I ◽

History Of

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Predictive fat mass equations for spinal muscular atrophy type I children: Development and internal validation

Clinical Nutrition ◽

10.1016/j.clnu.2021.02.026 ◽

2021 ◽

Vol 40 (4) ◽

pp. 1578-1587

Author(s):

Andrea Foppiani ◽

Ramona De Amicis ◽

Alessandro Leone ◽

Simone Ravella ◽

Giorgio Bedogni ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Fat Mass ◽

Muscular Atrophy ◽

Type I ◽

Internal Validation ◽

Spinal Muscular Atrophy Type ◽

Children Development

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SMN mRNA and protein levels in peripheral blood

Neurology ◽

10.1212/01.wnl.0000201929.56928.13 ◽

2006 ◽

Vol 66 (7) ◽

pp. 1067-1073 ◽

Cited By ~ 58

Author(s):

C. J. Sumner ◽

S. J. Kolb ◽

G. G. Harmison ◽

N. O. Jeffries ◽

K. Schadt ◽

...

Keyword(s):

Clinical Trials ◽

Spinal Muscular Atrophy ◽

Disease Severity ◽

Peripheral Blood ◽

Muscular Atrophy ◽

Gene Copy ◽

Blood Levels ◽

Type I ◽

Protein Levels ◽

Smn Protein

Background: Clinical trials of drugs that increase SMN protein levels in vitro are currently under way in patients with spinal muscular atrophy.Objective: To develop and validate measures of SMN mRNA and protein in peripheral blood and to establish baseline SMN levels in a cohort of controls, carriers, and patients of known genotype, which could be used to follow response to treatment.Methods: SMN1 and SMN2 gene copy numbers were determined in blood samples collected from 86 subjects. Quantitative reverse transcription PCR was used to measure blood levels of SMN mRNA with and without exon 7. A cell immunoassay was used to measure blood levels of SMN protein.Results: Blood levels of SMN mRNA and protein were measured with high reliability. There was little variation in SMN levels in individual subjects over a 5-week period. Levels of exon 7-containing SMN mRNA and SMN protein correlated with SMN1 and SMN2 gene copy number. With the exception of type I SMA, there was no correlation between SMN levels and disease severity.Conclusion: SMN mRNA and protein levels can be reliably measured in the peripheral blood and used during clinical trials in spinal muscular atrophy, but these levels do not necessarily predict disease severity.

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2020 Update to Spinal Muscular Atrophy Management in Saudi Arabia

Frontiers in Pediatrics ◽

10.3389/fped.2021.684134 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fahad A. Bashiri ◽

Mohamad-Hani Temsah ◽

Khalid Hundallah ◽

Fahad Alsohime ◽

Yazed AlRuthia

Keyword(s):

Gene Therapy ◽

Saudi Arabia ◽

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Management Strategies ◽

Annual Conference ◽

Type I ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Society Annual

Novel therapeutic strategies have shown some promise in treating spinal muscular atrophy (SMA). However, the outcomes and acceptance of these new strategies are yet to be explored. We aimed to investigate physicians' opinions and perceptions toward management strategies of SMA across Saudi Arabia. This is a cross-sectional survey using a self-administered, structured questionnaire sent to physicians who care for SMA patients during the Saudi Pediatric Neurology Society annual conference. A total of 72 clinicians of different neurological subspecialties were included. 48.6% prescribed nusinersen to their patients, with 39% of them having patients started on nusinersen. Though, 8.3% prescribed onasemnogene abeparvovec for 1–3 patients, while none of their patients started on the treatment. 64.3% stated that the only treatment available for SMA in their settings is supportive care. Around 69.4% described having a moderate to high knowledge on SMA gene therapy, and 79.2% would recommend it. 48.6% confirmed they would prescribe gene therapy at the age of 6 months, and 78.3% would prescribe it for type-I SMA. Pediatric neurologists are receptive to novel and innovative therapies for SMA in Saudi Arabia. However, the high treatment acquisition cost, strict regulations, logistical issues, and budget constraints delay their adoption and implementation.

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