Position Statement: Sharing of Clinical Research Data in Spinal Muscular Atrophy to Accelerate Research and Improve Outcomes for Patients.
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ABSTRACT:
SUBMITTER: Lochmuller H
PROVIDER: S-EPMC6004907 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Position Statement: Sharing of Clinical Research Data in Spinal Muscular Atrophy to Accelerate Research and Improve Outcomes for Patients.
Lochmüller Hanns H Evans David D Farwell Wildon W Finkel Richard R Goemans Nathalie N de Lemus Mencia M Matyushenko Vitaliy V Muntoni Francesco F Ouillade Marie-Christine MC Schwersenz Inge I Wilson Petra P
Journal of neuromuscular diseases 20180101 2
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Project description:Spinal muscular atrophy (SMA) is a potentially devastating and lethal neuromuscular disease frequently manifesting in infancy and childhood. The discovery of the underlying mutation in the survival of motor neurons 1 (SMN1) gene has accelerated preclinical research, leading to treatment targets and transgenic mouse models, but there is still no effective treatment. The clinical severity is inversely related to the copy number of SMN2, a modifying gene producing some full-length SMN transcript. Drugs shown to increase SMN2 function in vitro, therefore, have the potential to benefit patients with SMA. Because several drugs are now on the horizon of clinical investigation, we review recent clinical trials for SMA and discuss the challenges and opportunities associated with SMA drug development. Although an orphan disease, SMA is well-positioned for successful trials given that it has a common genetic etiology in most cases, that it can be readily diagnosed, that preclinical research in vitro and in transgenic animals has identified candidate compounds, and that trial networks have been established.
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Project description:Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq In total 12 samples were analyzed, divided into four distinct groups (treated with SMN-C3 @ 500 nM; controls for SMN-C3; treated with SMN-C1 @ 100 nM; controls for SMN-C1) containing 3 replicates each.
2014-10-22 | E-GEOD-62540 | biostudies-arrayexpress
Project description:Characterization of the selectivity of SMN splicing modifiers in SMA type I fibroblasts by RNASeq
2014-10-22 | GSE62540 | GEO
Project description:BackgroundNovel Spinal Muscular Atrophy (SMA) treatments have demonstrated improvements on motor measures that are clearly distinct from the natural history of progressive decline. Comparable measures are needed to monitor bulbar function, which is affected in severe SMA.ObjectiveTo assess bulbar function with patient-reported outcome measures (PROs) and determine their relationships with clinical characteristics.MethodsWe recruited 47 non-ambulatory participants (mean (SD) age = 29.8 (13.7) years, range = 10.3-73.2) with SMA. PROs including Voice Handicap Index (VHI) and Eating Assessment Tool-10 (EAT-10) were collected alongside clinical characteristics and standardized motor assessments. Associations were assessed using Spearman correlation coefficients and group comparisons were performed using Wilcoxon rank sum tests.ResultsA majority of the 47 participants were SMA type 2 (70.2%), non-sitters (78.7%), 3 copies of SMN2 (77.5%), and using respiratory support (66.0%). A majority (94%) reported voice issues primarily in 8/30 VHI questions. Problems included: difficulty understanding me in a noisy room (87.2%); difficult for people to hear me (74.5%); and people ask me to repeat when speaking face-to-face (72.3%). A majority (85.1%) reported swallowing issues primarily in 3/10 EAT-10 questions: swallowing pills (68.1%); food sticks to my throat (66.0%); and swallowing solids (61.7%). The two PROs were moderately associated (rs = 0.66).ConclusionsWeaker individuals with SMA experience bulbar problems including difficulties with voice and swallowing. Further refinement and assessment of functional bulbar scales will help determine their relevance and responsiveness to changes in SMA. Additional study is needed to quantify bulbar changes caused by SMA and their response to disease-modifying treatments.
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