Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy.

Objective: To report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping.

Methods: Part 1 was a randomized, double-blind, placebo-controlled, 12-week dose titration of once-weekly golodirsen; part 2 is an ongoing, open-label evaluation. Safety and pharmacokinetics were primary and secondary objectives of part 1.

Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy.

This analysis aims to describe the outcomes of two nonambulatory patients with Duchenne muscular dystrophy (DMD) who participated in two clinical studies. The two consecutive trials of eteplirsen (studies 201 and 202) were conducted in patients with DMD (N = 12) and confirmed genetic mutations amenable to exon 51 skipping.In study 201, 12 patients were randomized to receive once-weekly, double-blind intravenous infusions of eteplirsen 30 or 50 mg/kg or placebo for 24 weeks; patients then received open-label eteplirsen during weeks 25 through 28.

Validation of a Muscle-Specific Tissue Image Analysis Tool for Quantitative Assessment of Dystrophin Staining in Frozen Muscle Biopsies.

Context.—: Duchenne muscular dystrophy is a rare, progressive, and fatal neuromuscular disease caused by dystrophin protein loss. Common investigational treatment approaches aim at increasing dystrophin expression in diseased muscle.

Low-level dystrophin expression attenuating the dystrophinopathy phenotype.

The reading frame rule suggests that Duchenne muscular dystrophy (DMD) results from DMD mutations causing an out-of-frame transcript, whereas the milder Becker muscular dystrophy results from mutations causing an in-frame transcript. However, predicted nonsense mutations may instead result in altered splicing and an in-frame transcript. Here we report a 10-year-old boy with a predicted nonsense mutation in exon 42 who had a 6-minute walk time of 157% of that of age matched DMD controls, characterized as intermediate muscular dystrophy.

Basal prostate epithelial cells stimulate the migration of prostate cancer cells.

Carcinoma cells in PIN are situated above a layer of basal epithelial cells, which shield the tumor cells from stimulation by factors from the prostate stroma. During progression to invasive carcinoma, the basal cell layer becomes disrupted and tumor cells adhere to the basement membrane. The close proximity of basal epithelial cells to tumor cells in the early stages of prostate oncogenesis raises the possibility that basal epithelial cells participate in tumor cell invasion.

Laminin 5 deposition regulates keratinocyte polarization and persistent migration.

Repair of wounded epidermis requires both keratinocyte migration and deposition of laminin 5 over exposed dermal collagen. To understand the coupling between leading cell migration and laminin 5 deposition, we developed a novel migration assay using time-lapse microscopy. We demonstrate that in migrating, human keratinocytes the deposition of laminin 5 promoted 'processive migration', characterized by stable cell polarization that was tightly coupled to persistent, linear migration in the absence of a chemotactic gradient.