Natural history of SMA IIIb

Deymeer, Feza; Serdaroğlu, Pıraye; Parman, Yeşim; Poda, Mehveş

doi:10.1212/01.wnl.0000324623.89105.c4

Cited by 54 publications

(59 citation statements)

References 22 publications

(17 reference statements)

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“…28 We did not observe significant progression of muscle weakness as previously described. 29 This may reflect different populations (SMA 3 with onset after 3 years of age only), different measurement techniques (manual muscle testing of multiple muscles), or a longer observation period (up to 20 years) in the previous report. Our findings suggest that the observed functional declines are the net result of a failure to gain sufficient strength and muscle mass to meet the increasing demands associated with normal growth and development.…”

Section: Discussionmentioning

confidence: 94%

Prospective cohort study of spinal muscular atrophy types 2 and 3

et al. 2012

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Objective: To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning. Methods:We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months. Clinically, we evaluated motor and pulmonary function, quality of life, and muscle strength. We also measured SMN2 copy number, hematologic and biochemical profiles, muscle mass by dual x-ray absorptiometry (DXA), and the compound motor action potential (CMAP) in a hand muscle. Data were analyzed for associations between clinical and biological/laboratory characteristics cross-sectionally, and for change over time in outcomes using all available data. Results:In cross-sectional analyses, certain biological measures (specifically, CMAP, DXA fatfree mass index, and SMN2 copy number) and muscle strength measures were associated with motor function. Motor and pulmonary function declined over time, particularly at time points beyond 12 months of follow-up. Conclusion:

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Section: Discussionmentioning

confidence: 94%

Prospective cohort study of spinal muscular atrophy types 2 and 3

et al. 2012

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“…SMN expression is probably highest in the embryonic period and declines after birth [43, 68, 69]. It is not known whether a continuing decline with age could contribute to the slow deterioration of motor function that has been observed in adult patients[70, 71]. Another explanation may lie in changes in the relative PBMC composition during life [72].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of SMN Protein and mRNA in Blood and Fibroblasts in Patients with Spinal Muscular Atrophy and Healthy Controls

et al. 2016

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BackgroundClinical trials to test safety and efficacy of drugs for patients with spinal muscular atrophy (SMA) are currently underway. Biomarkers that document treatment-induced effects are needed because disease progression in childhood forms of SMA is slow and clinical outcome measures may lack sensitivity to detect meaningful changes in motor function in the period of 1–2 years of follow-up during randomized clinical trials.ObjectiveTo determine and compare SMN protein and mRNA levels in two cell types (i.e. PBMCs and skin-derived fibroblasts) from patients with SMA types 1–4 and healthy controls in relation to clinical characteristics and SMN2 copy numbers.Materials and methodsWe determined SMN1, SMN2-full length (SMN2-FL), SMN2-delta7 (SMN2-Δ7), GAPDH and 18S mRNA levels and SMN protein levels in blood and fibroblasts from a total of 150 patients with SMA and 293 healthy controls using qPCR and ELISA. We analyzed the association with clinical characteristics including disease severity and duration, and SMN2 copy number.ResultsSMN protein levels in PBMCs and fibroblasts were higher in controls than in patients with SMA (p<0.01). Stratification for SMA type did not show differences in SMN protein (p>0.1) or mRNA levels (p>0.05) in either cell type. SMN2 copy number was associated with SMN protein levels in fibroblasts (p = 0.01), but not in PBMCs (p = 0.06). Protein levels in PBMCs declined with age in patients (p<0.01) and controls (p<0.01)(power 1-beta = 0.7). Ratios of SMN2-Δ7/SMN2-FL showed a broad range, primarily explained by the variation in SMN2-Δ7 levels, even in patients with a comparable SMN2 copy number. Levels of SMN2 mRNA did not correlate with SMN2 copy number, SMA type or age in blood (p = 0.7) or fibroblasts (p = 0.09). Paired analysis between blood and fibroblasts did not show a correlation between the two different tissues with respect to the SMN protein or mRNA levels.ConclusionsSMN protein levels differ considerably between tissues and activity is age dependent in patients and controls. SMN protein levels in fibroblasts correlate with SMN2 copy number and have potential as a biomarker for disease severity.

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“…Open label studies have reported a functional improvement of some SMA patients after treatment with VPA,9 10 but the selection of meaningful clinical outcome measures to determine efficacy of experimental therapy in SMA is complicated by the very slow progression following onset 9 11 12. SMN quantification techniques may therefore be helpful additional tools to investigate experimental treatment effects.…”

Section: Discussionmentioning

confidence: 99%