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Research on Duchenne muscular dystrophy

Koot, M.V. (2016) Research on Duchenne muscular dystrophy. Bachelor's Thesis, Biology.

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Abstract

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease with an incidence of 3500-5000 male live births. The DMD gene is the biggest human gene and because of this, it is sensitive to mutations. The DMD gene encodes for the dystrophin protein and, thus, this protein is absent in DMD patients. As a result, muscle fibers are easily damaged during contraction, leading to inflammation, chronic muscle damage and eventually replacement of muscle fibers by fat and fibrotic tissue and, therefore, loss of muscle function. A lot of research on DMD has been performed and is still being performed. In this review, different types of research on DMD are addressed: nutrition considerations, drug treatment, rehabilitation, medical devices, cell-based therapy, gene therapy and strategies to correct the mutated gene. Currently, the most promising therapy for treating DMD is exon skipping. Exon skipping is accomplished by using antisense oligonucleotides (AONs). For skipping exon 51, two types of AONs are being studied: 2’-O-methyl phosphorotioates (2’OMePs) and phosphorodiamidate morpholino oligomers (PMOs). Drisapersen is a 2’OMeP AON and has completed up to phase III clinical trials. Unfortunately, the FDA rejected application for market authorization and partly because of this, the application for the European market was withdrawn. All clinical trials and development were discontinued. Another exon skipping drug is currently still being developed: eteplirsen, a PMO AON. A phase II clinical trial shows significant improvements in the 6MWD test after 36 months. A phase III clinical trial is currently ongoing, so no results have been published yet. Also, the FDA is currently reviewing the application of this drug. PMO AONs appear to be more favorable and less toxic than 2’OMeP AONs, because of their backbone chemistry. Therefore, whether eteplirsen is getting approved or not, exon skipping studies should focus more on PMO AONs.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:14
Last Modified: 15 Feb 2018 08:14
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/14220

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