Arash Salmaninejad1,2,3, Saeed Farajzadeh Valilou4, Hadi Bayat5, Nader Ebadi6, Abdolreza Daraei7, Meysam Yousefi2,3, Abolfazl Nesaei8, Majid Mojarrad2,3. 1. a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran. 2. b Student Research Committee, Department of Medical Genetics, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran. 3. c Medical Genetics Research Center, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran. 4. d Medical Genetics Network (MeGeNe) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran. 5. e Department of Tissue Engineering, School of Advanced Technologies in Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran. 6. f Department of Medical Genetics, Faculty of Medicine , Tehran University of Medical Science , Tehran , Iran. 7. g Genetic Department, Faculty of Medicine , Babol University of Medical Sciences , Babol , Iran. 8. h Department of Basic Sciences, Faculty of Medicine , Gonabad University of Medical Sciences , Gonabad , Iran.
Abstract
BACKGROUND AND PURPOSE: Duchenne muscular dystrophy (DMD) is a lethal progressive pediatric muscle disorder and genetically inherited as an X-linked disease that caused by mutations in the dystrophin gene. DMD leads to progressive muscle weakness, degeneration, and wasting; finally, follows with the premature demise in affected individuals due to respiratory and/or cardiac failure typically by age of 30. For decades, scientists tried massively to find an effective therapy method, but there is no absolute cure currently for patients with DMD, nevertheless, recent advanced progressions on the treatment of DMD will be hopeful in the future. Several promising gene therapies are currently under investigation. These include gene replacement, exon skipping, suppression of stop codons. More recently, a promising gene editing tool referred to as CRISPR/Cas9 offers exciting perspectives for restoring dystrophin expression in patients with DMD. This review intents to briefly describe these methods and comment on their advances. Since DMD is a genetic disorder, it should be treated by replacing the deficient DMD copy with a functional one. However, there are different types of mutations in this gene, so such therapeutic approaches are highly mutation specific and thus are personalized. Therefore, DMD has arisen as a model of genetic disorder for understanding and overcoming of the challenges of developing personalized genetic medicines, consequently, the lessons learned from these approaches will be applicable to many other disorders. CONCLUSIONS: This review provides an update on the recent gene therapies for DMD that aim to compensate for dystrophin deficiency and the related clinical trials.
BACKGROUND AND PURPOSE:Duchenne muscular dystrophy (DMD) is a lethal progressive pediatric muscle disorder and genetically inherited as an X-linked disease that caused by mutations in the dystrophin gene. DMD leads to progressive muscle weakness, degeneration, and wasting; finally, follows with the premature demise in affected individuals due to respiratory and/or cardiac failure typically by age of 30. For decades, scientists tried massively to find an effective therapy method, but there is no absolute cure currently for patients with DMD, nevertheless, recent advanced progressions on the treatment of DMD will be hopeful in the future. Several promising gene therapies are currently under investigation. These include gene replacement, exon skipping, suppression of stop codons. More recently, a promising gene editing tool referred to as CRISPR/Cas9 offers exciting perspectives for restoring dystrophin expression in patients with DMD. This review intents to briefly describe these methods and comment on their advances. Since DMD is a genetic disorder, it should be treated by replacing the deficient DMD copy with a functional one. However, there are different types of mutations in this gene, so such therapeutic approaches are highly mutation specific and thus are personalized. Therefore, DMD has arisen as a model of genetic disorder for understanding and overcoming of the challenges of developing personalized genetic medicines, consequently, the lessons learned from these approaches will be applicable to many other disorders. CONCLUSIONS: This review provides an update on the recent gene therapies for DMD that aim to compensate for dystrophin deficiency and the related clinical trials.
Authors: Lee A Campbell; Lamarque M Coke; Christopher T Richie; Lowella V Fortuno; Aaron Y Park; Brandon K Harvey Journal: Mol Ther Date: 2018-10-11 Impact factor: 11.454
Authors: Nicole A Datson; Suzanne Bijl; Anneke Janson; Janwillem Testerink; Rani van den Eijnde; Rudie Weij; Jukka Puoliväli; Kimmo Lehtimäki; Timo Bragge; Toni Ahtoniemi; Judith C van Deutekom Journal: Nucleic Acid Ther Date: 2019-12-10 Impact factor: 5.486