scholarly journals Digital Droplet PCR for the Absolute Quantification of Exon Skipping Induced by Antisense Oligonucleotides in (Pre-)Clinical Development for Duchenne Muscular Dystrophy

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162467 ◽  
Author(s):  
Ruurd C. Verheul ◽  
Judith C. T. van Deutekom ◽  
Nicole A. Datson
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotides ◽  
Exon Skipping ◽  
Absolute Quantification ◽  
Clinical Development ◽  
Digital Droplet Pcr ◽  
Droplet Pcr ◽  
The Absolute

In vivocomparison of 2′-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping

2009 ◽  
Vol 11 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Hans A. Heemskerk ◽  
Christa L. de Winter ◽  
Sjef J. de Kimpe ◽  
Petra van Kuik-Romeijn ◽  
Niki Heuvelmans ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotides ◽  
Exon Skipping

scholarly journals Novel Cationic Carotenoid Lipids as Delivery Vectors of Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy

Molecules ◽  
2012 ◽  
Vol 17 (2) ◽  
pp. 1138-1148 ◽  
Author(s):  
Linda J. Popplewell ◽  
Aseel Abu-Dayya ◽  
Tushar Khanna ◽  
Marcella Flinterman ◽  
Nada Abdul Khalique ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotides ◽  
Exon Skipping

scholarly journals Exon-Skipping in Duchenne Muscular Dystrophy

2021 ◽  
pp. 1-16
Author(s):  
Shin’ichi Takeda ◽  
Paula R. Clemens ◽  
Eric P. Hoffman
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Drug Development ◽  
Rare Disease ◽  
19Th Century ◽  
Exon Skipping ◽  
Clinical Development ◽  
Therapeutic Development ◽  
The 19Th Century

Duchenne muscular dystrophy (DMD) is a devastating, rare disease. While clinically described in the 19th century, the genetic foundation of DMD was not discovered until more than 100 years later. This genetic understanding opened the door to the development of genetic treatments for DMD. Over the course of the last 30 years, the research that supports this development has moved into the realm of clinical trials and regulatory drug approvals. Exon skipping to therapeutically restore the frame of an out-of-frame dystrophin mutation has taken center stage in drug development for DMD. The research reviewed here focuses on the clinical development of exon skipping for the treatment of DMD. In addition to the generation of clinical treatments that are being used for patient care, this research sets the stage for future therapeutic development with a focus on increasing efficacy while providing safety and addressing the multi-systemic aspects of DMD.

scholarly journals Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy

2018 ◽  
Vol 26 (1) ◽  
pp. 132-147 ◽  
Author(s):  
Silvana M.G. Jirka ◽  
Peter A.C. ’t Hoen ◽  
Valeriano Diaz Parillas ◽  
Christa L. Tanganyika-de Winter ◽  
Ruurd C. Verheul ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Antisense Oligonucleotides ◽  
Cyclic Peptides ◽  
Exon Skipping

The Pharmacokinetics of 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides: Experiences from Developing Exon Skipping Therapies for Duchenne Muscular Dystrophy

2019 ◽  
Vol 29 (6) ◽  
pp. 305-322 ◽  
Author(s):  
Sieto Bosgra ◽  
Jessica Sipkens ◽  
Sjef de Kimpe ◽  
Cathaline den Besten ◽  
Nicole Datson ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotides ◽  
Exon Skipping

scholarly journals New Approach for Antisense Oligonucleotide-Mediated Exon Skipping in Duchenne Muscular Dystrophy

2012 ◽  
Vol 16 (4) ◽  
pp. 521-526
Author(s):  
Yoshitsugu Aoki ◽  
◽  
Tetsuya Nagata ◽  
Shin’ichi Takeda
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Exon Skipping ◽  
New Approach ◽  
Reading Frame ◽  
Promising Therapeutic Approach ◽  
Dmd Gene ◽  
Dystrophin Protein

Duchenne Muscular Dystrophy (DMD) is a lethalmuscle disorder characterized by mutations in the DMD gene. These mutations primarily disrupt the reading frame, resulting in the absence of functional dystrophin protein. Exon skipping, which involves the use of antisense oligonucleotides is a promising therapeutic approach for DMD, and clinical trials on exon skipping are currently underway in DMD patients. Recently, stable and less-toxic antisense oligonucleotides with higher efficacy have been developed in mouse and dog models of DMD. This review highlights a new approach for antisense oligonucleotide-based therapeutics for DMD, particularly for exon skipping-based methods.

scholarly journals Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy

2021 ◽  
Vol 12 ◽  
Author(s):  
Theodora Markati ◽  
Liesbeth De Waele ◽  
Urlike Schara-Schmidt ◽  
Laurent Servais
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Life Expectancy ◽  
Late Phase ◽  
Unmet Need ◽  
Exon Skipping ◽  
Clinical Development ◽  
Lessons Learned ◽  
Attrition Rate ◽  
Standards Of Care

Duchenne muscular dystrophy (DMD) is an X-linked condition caused by a deficiency of functional dystrophin protein. Patients experience progressive muscle weakness, cardiomyopathy and have a decreased life expectancy. Standards of care, including treatment with steroids, and multidisciplinary approaches have extended the life expectancy and improved the quality of life of patients. In the last 30 years, several compounds have been assessed in preclinical and clinical studies for their ability to restore functional dystrophin levels or to modify pathways involved in DMD pathophysiology. However, there is still an unmet need with regards to a disease-modifying treatment for DMD and the attrition rate between early-phase and late-phase clinical development remains high. Currently, there are 40 compounds in clinical development for DMD, including gene therapy and antisense oligonucleotides for exon skipping. Only five of them have received conditional approval in one jurisdiction subject to further proof of efficacy. In this review, we present data of another 16 compounds that failed to complete clinical development, despite positive results in early phases of development in some cases. We examine the reasons for the high attrition rate and we suggest solutions to avoid similar mistakes in the future.

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