Myology research highlights

The prevailing pathomechanistic paradigm for myotonic dystrophy (DM) is that aberrant expression of embryonic/fetal mRNA/protein isoforms accounts for most aspects of the pleiotropic phenotype. To identify aberrant isoforms in skeletal muscle of DM1 and DM2 patients, the authors performed exon-array profiling and RT-PCR validation on the largest DM sample set to date, including Duchenne, Becker … [Read more]

Myotonic dystrophy (DM) of type 1 and 2 (DM1 and DM2) are inherited autosomal dominant diseases caused by dynamic and unstable expanded microsatellite sequences (CTG and CCTG, respectively) in the non-coding regions of the genes DMPK and ZNF9, respectively. These mutations result in the intranuclear accumulation of mutated transcripts and the mis-splicing of numerous transcripts. … [Read more]

In this study, the effects of pain site and intensity on function were examined in patients with myotonic dystrophy type 1 (DM1) and facioscapulohumeral muscular dystrophy (FSHD) and chronic pain. Questionnaires assessing pain sites, pain extent (number of sites), pain intensity, and pain interference were completed by 182 individuals with DM1 (43%) or FSHD (57%) … [Read more]

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are progressive multisystemic disorders caused by similar mutations at two different genetic loci. The common key feature of DM pathogenesis is nuclear accumulation of mutant RNA which causes aberrant alternative splicing of specific pre-mRNAs by altering the functions of two RNA binding proteins, MBNL1 and CUGBP1. … [Read more]

The socal context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for … [Read more]

Antisense oligonucleotide (AON)-mediated exon skipping is a promising therapeutic approach for Duchenne muscular dystrophy (DMD) that is currently being tested in various clinical trials. This approach is based on restoring the open reading frame of dystrophin transcripts resulting in shorter but partially functional dystrophin proteins as found in patients with Becker muscular dystrophy. After systemic … [Read more]

Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2′-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after … [Read more]

Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124) enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. This Phase 2a open-label, sequential … [Read more]

Most pathogenic mutations in Duchenne and Becker muscular dystrophies involve deletion of single or multiple exons from the dystrophin gene, so exon-specific monoclonal antibodies (mAbs) can be used to distinguish normal and mutant dystrophin proteins. In Duchenne therapy trials, mAbs can be used to identify or rule out dystrophin-positive “revertant” fibres, which have an internally-deleted … [Read more]

Congenital muscular dystrophy Type 1A (MDC1A) is a severe, recessive disease of childhood onset that is caused by mutations in the LAMA2 gene encoding laminin-alpha2. Studies with both mouse models and primary cultures of human MDC1A myogenic cells suggest that aberrant activation of cell death is a significant contributor to pathogenesis in laminin-alpha2-deficiency. To overcome … [Read more]