The 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.
Evidence-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.
Improved Methods for Reprogramming Human Dermal Fibroblasts Using Fluorescence Activated Cell Sorting
A team of the New York Stem Cell Foundation (NYSCF) Research Institute have recently developed a new way to generate induced pluripotent stem (iPS) cell lines from human fibroblasts, acquired from both healthy and diseased donors. The technique utilizes fluorescence activated cell sorting to quantify two specific markers of pluripotency, and “the protocol has enabled […]
DMD 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.
Summit Outlines Clinical Development Plans for Utrophin Modulator Programme for Duchenne Muscular Dystrophy
Summit Corporation plc (‘Summit’ or ‘the Company’) SUMMIT OUTLINES CLINICAL DEVELOPMENT PLANS FOR UTROPHIN MODULATOR PROGRAMME FOR DUCHENNE MUSCULAR DYSTROPHY First patient clinical trials of SMT C1100 expected to start H2 2013 Summit to showcase programme at international scientific conference Oxford, UK, 21 March 2013 – Summit (AIM: SUMM), a drug discovery and development company […]
All-Cause Mortality and Cardiovascular Outcomes With Prophylactic Steroid Therapy in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) patients suffer from cardiorespiratory complications in which progressive respiratory failure is the most common cause of mortality, and cardiomyopathy accounts for 20%-40% of all deaths. Inhibitors of the renin-angiotensin-aldosterone system (with or without beta blockers) are used clinically to delay progressive ventricular dysfunction.
Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy
The use of antisense oligonucleotides (AON) to induce exon skipping in precursor mRNA is at the forefront of clinical research for the treatment of DMD. The most advanced programs from Sarepta Therapeutics and GSK/Prosensa target exon 51, and are currently in Phase II and Phase III clinical trails in the US and the rest of the world. Their approval is anticipated within the near future.
Strategies that could enhance or improve the efficiency of the current (and future) exon skipping drugs to produce novel dystrophin have been sought by a number of research groups over the last few years. Now a recent report by Kendall et al. describes the identification of a compound that enhances the efficiency of exon skipping in vitro and in vivo. The compound, the approved drug Dantrolene, works in concert with the exon skipping drug to restore dystrophin levels in the mdxmice and also in reprogrammed myotubes from DMD patients. This research offers insight into the exon skipping process, and could provide a fast track opportunity to use an approved drug to enhance the efficiency of current exon skipping drugs in future clinical trials.
A recent placebo-controlled clinical study on the effects of the PDE5A inhibitor drug Tadalafil (Cialis), demonstrated beneficial effects on muscle blood flow in a model of muscle ischemia in men with Becker muscular dystrophy who harbor a mutation in which the neuronal nitric oxide synthase is absent. The result reinforce earlier findings in mice and Duchene patients and highlight the role of this pathway in muscle homeostasis.
Directors of the California stem cell agency today deferred action on a $20 million proposal that was rejected by its grant reviewers and sent it back for more consideration.
Sarepta Therapeutics Announces Significant Clinical Benefit With Eteplirsen After 36 Weeks in Phase IIb Study for the Treatment of Duchenne Muscular Dystrophy
Sarepta Therapeutics (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced that treatment with its exon-skipping compound, eteplirsen, achieved a significant clinical benefit on the primary clinical outcome, the 6-minute walk test (6MWT), over a placebo/delayed treatment cohort in a Phase IIb trial in Duchenne muscular dystrophy (DMD) patients.