Articles
Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy
April 9, 2013The purpose of the study is to see whether PRO045 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 45 in the DNA for the dystrophin protein.
Read moreReview of Phase II and Phase III Clinical Trials for Duchenne Muscular Dystrophy
April 1, 2013Evidence-based therapeutics in Duchenne muscular dystrophy (DMD) has been limited to corticosteroids for the past 30 years. There have been a host of other therapeutic interventions studied in mice, canines and more recently humans, but they are yet to show effectiveness in clinical trials. Newer genetic approaches are in early stages of clinical trials.
Read moreInterplay between DMD Point Mutations and Splicing Signals in Dystrophinopathy Phenotypes.
March 25, 2013DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements.
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