Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

D’Amario, Domenico; Gowran, Aoife; Canonico, Francesco; Castiglioni, Elisa; Rovina, Davide; Santoro, Rosaria; Spinelli, Pietro; Adorisio, Rachele; Amodeo, Antonio; Perrucci, Gianluca Lorenzo; Borovac, Josip Anđelo; Pompilio, Giulio; Crea, Filippo

doi:10.3390/jcm7090291

“…The nitrogenous bases are incorporated on a morpholine six-membered Golodirsen was developed for the treatment of Duchenne's muscular dystrophy (DMD), which is a progressive muscle deterioration that starts in early childhood and in most cases ends up crippling patients before adolescence. After several years, patients die mainly from heart failure [7,8]. This disorder is caused by a deletion mutation in the dystrophin gene, which transcribes for the production of dystrophin, a huge protein that covers muscular fibers, protecting them from damage upon contraction and enhancing muscle performance.…”

Section: Golodirsen (Vyondys 53 Tm )mentioning

confidence: 99%

“…The genetic disorder causes the production of a non-functioning dystrophin protein and consequently muscle wasting. This gene is linked to the X chromosome, thus making DMD disorder more noticeable in male infants [7,9].…”

Section: Golodirsen (Vyondys 53 Tm )mentioning

confidence: 99%

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2019 FDA TIDES (Peptides and Oligonucleotides) Harvest

Shaer

¹

,

Musaimi

²

,

Alberício

³

et al. 2020

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2019 has been an excellent year in terms of peptides and oligonucleotides (TIDES) approved by the FDA. Despite the drop in the number of total drugs approved by the FDA in 2019 in comparison with 2018 (48 vs. 59), the total number of TIDES authorized increased (seven vs. three). Year after year, TIDES are increasingly present in therapy, as imaging agents, theragnostic and constituent moieties of other complex drugs, such as antibody drug conjugates. This means a consolidation of these kinds of drugs in the pharmaceutical arena, paving the way in the coming years for the approval of others for diverse medical indications. Here the TIDES approved in 2019 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects.

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“…The cardiomyopathy in DMD manifests as DCM and develops in three stages [43]. In the first stage, occurring before the teens, DMD patients show no symptoms of heart failure.…”

Section: Cardiomyopathy In Dmd and Other Disordersmentioning

confidence: 99%

Genome Editing for the Understanding and Treatment of Inherited Cardiomyopathies

Nguyen

¹

,

Lim

²

,

Yokota

³

2020

IJMS

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Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

show abstract

“…The cardiomyopathy in DMD manifests as DCM and develops in three stages [51]. In the first stage, occurring before the teens, DMD patients show no symptoms of heart failure.…”

Section: Cardiomyopathy In Dmd and Other Disordersmentioning

confidence: 99%

Genome Editing for the Understanding and Treatment of Cardiomyopathies

Nguyen¹,

Lim²,

Yokota³

2019

Preprint

0

View full text Add to dashboard Cite

Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.Keywords: dilated cardiomyopathy (DCM); hypertrophic cardiomyopathy (HCM); restrictive cardiomyopathy (RCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); left ventricular non-compaction cardiomyopathy (LVNC); Duchenne muscular dystrophy; dystrophin; genome editing; CRISPR/Cas9; Cpf1 (Cas12a) Cardiomyopathy is also a major manifestation in a subset of neuromuscular disorders [7,8]. Cardiomyopathy is most commonly associated with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), both X-linked recessive disorders caused by mutations in the dystrophin (DMD) gene [8]. DMD codes for dystrophin, a cytoskeletal protein that maintains the Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: structural integrity of muscle fibres during contraction-relaxation cycles. Loss-of-function mutations in the DMD gene result in an absence of dystrophin, leading to DMD [9][10][11]. Mutations maintaining the DMD reading frame produce truncated but partly functional dystrophin, and often result in a milder form of the disease known as BMD [12,13]. Cardiomyopathy is a leading cause of death in both DMD and BMD patients and is routinely described as being DCM [13,14]. Other neuromuscular disorders associated with cardiomyopathy include the limb girdle muscle dystrophies, myotonic dystrophy, and Friedreich ataxia [15].Advances in molecular genetics enable genome editing to be incorporated into various fields of biomedical research, including the cardiovascular sciences. Currently, the most commonly used tools are zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) [16]. Both ZFNs and TALENs are engineered restriction enzymes created by combining a DNA binding domain with a DNA cleavage domain adapted from the FokI restriction enzyme [17][18][19]. The DNA binding domain in Z...

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Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

Cited by 24 publications

References 240 publications

2019 FDA TIDES (Peptides and Oligonucleotides) Harvest

2019 FDA TIDES (Peptides and Oligonucleotides) Harvest

Genome Editing for the Understanding and Treatment of Inherited Cardiomyopathies

Genome Editing for the Understanding and Treatment of Cardiomyopathies

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