209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7–9 November 2014, Heemskerk, The Netherlands

Finkel, Richard S.; Bertini, Enrico; Muntoni, Francesco; Mercuri, Eugenio

doi:10.1016/j.nmd.2015.04.009

Cited by 175 publications

(210 citation statements)

References 64 publications

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“…The diagnosis of SMA was made by the principal investigator at each site who also classified them according to the Dubowitz's decimal classification [11] and to the recently proposed classification in 3 subtypes [4], [12]: type IA presentation at birth with joint contractures and need for respiratory support, or onset of motor and respiratory involvement in the first week; type IB, symptom onset after neonatal period, usually before age 3 months, head control never achieved; and type IC, onset after neonatal period, usually between 3 and 6 months, head control achieved.…”

Section: Methodsmentioning

confidence: 99%

Developmental milestones in type I spinal muscular atrophy

Sanctis

Coratti

Pasternak

et al. 2016

Neuromuscular Disorders

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Section: Methodsmentioning

confidence: 99%

Developmental milestones in type I spinal muscular atrophy

Sanctis

Coratti

Pasternak

et al. 2016

Neuromuscular Disorders

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108

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“…Electrophysiological outcomes compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE) correlate with age, SMA type, functional status, and SMN2 copy number 11. Gradual decline in motor and respiratory function may, in part, be related to physical growth in SMA types II and III, with the provision that CMAP amplitude remains stable 9. In addition, the CMAP amplitude may also remain constant despite reduction in MUNE values, a finding explained by the presence of motor unit loss with compensatory collateral sprouting and supported by axonal excitability studies 12.…”

Section: Progress In Understanding the Natural History Of Smamentioning

confidence: 99%

Emerging therapies and challenges in spinal muscular atrophy

Farrar

Park

Vucic

et al. 2017

Annals of Neurology

193

170

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Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease‐modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease‐modifying therapies will necessitate monitoring programs to determine the long‐term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355–368

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“…However, these phenotypes are seen more as a continuum rather than as distinct subtypes and sometimes further subtypes at both ends of the spectrum are observed. SMA type 0 is a very severe form with onset in utero, reduced or absent movements, contractures, and requirement for mechanical ventilation support at birth and death before six months of age, while SMA type IV is a mild late (adult) onset form that has a normal life expectancy [1, 2]. An overview of the different subtypes is given in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy – a literature review

Verhaart

Robertson

Wilson

et al. 2017

Orphanet J Rare Dis

493

389

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Spinal muscular atrophy linked to chromosome 5q (SMA) is a recessive, progressive, neuromuscular disorder caused by bi-allelic mutations in the SMN1 gene, resulting in motor neuron degeneration and variable presentation in relation to onset and severity. A prevalence of approximately 1–2 per 100,000 persons and incidence around 1 in 10,000 live births have been estimated with SMA type I accounting for around 60% of all cases. Since SMA is a relatively rare condition, studies of its prevalence and incidence are challenging. Most published studies are outdated and therefore rely on clinical rather than genetic diagnosis. Furthermore they are performed in small cohorts in small geographical regions and only study European populations. In addition, the heterogeneity of the condition can lead to delays and difficulties in diagnosing the condition, especially outside of specialist clinics, and contributes to the challenges in understanding the epidemiology of the disease. The frequency of unaffected, heterozygous carriers of the SMN1 mutations appears to be higher among Caucasian and Asian populations compared to the Black (Sub-Saharan African ancestry) population. However, carrier frequencies cannot directly be translated into incidence and prevalence, as very severe (death in utero) and very mild (symptom free in adults) phenotypes carrying bi-allelic SMN1 mutations exist, and their frequency is unknown.More robust epidemiological data on SMA covering larger populations based on accurate genetic diagnosis or newborn screening would be helpful to support planning of clinical studies, provision of care and therapies and evaluation of outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0671-8) contains supplementary material, which is available to authorized users.

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209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7–9 November 2014, Heemskerk, The Netherlands

Cited by 175 publications

References 64 publications

Developmental milestones in type I spinal muscular atrophy

Developmental milestones in type I spinal muscular atrophy

Emerging therapies and challenges in spinal muscular atrophy

Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy – a literature review

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