Treatment with Ataluren for Duchene Muscular Dystrophy

Morkous, Sameh S

doi:10.15844/pedneurbriefs-34-12

Cited by 10 publications

(5 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Клинические исследования (NCT04336826, NCT03179631, NCT02369731) аталурена в терапии МДД продолжаются. Результаты более чем 6-летнего ретроспективного исследования с включением 11 [29][30][31]. В настоящее время для аталурена продлено условное одобрение от Европейского агентства лекарственных средств (EMA).…”

Section: развитие этиотропных подходов к терапии миодистрофии дюшеннаunclassified

Stages of research and development of therapeutic approaches for Duchenne myodystrophy. Part II: etiotropic approaches

Kochergin-Nikitskiy,

Smirnikhina,

Lavrov

2024

Neuromuscular Diseases

View full text Add to dashboard Cite

Duchenne muscular dystrophy is one of the most common inherited muscular dystrophies. The cause of this disease with an X‑linked recessive type of inheritance is mutations in the DMD gene, leading to the absence of the dystrophin protein this gene encodes or its impaired function. Loss of dystrophin leads to severe degenerative processes in patients, especially in muscle tissue, with impaired muscle function, loss of ability to move independently, respiratory failure, cardiomyopathies, etc.The collective efforts of many researchers over the years since the 19th century, when the diseases was described, not allowed to achieve a cure or significantly influencing the trajectory of the illness. The only notable impact on the disease course has come with the integration of corticosteroid medications into Duchenne muscular dystrophy therapy. While their application can decelerate disease progression and extend the average life expectancy up to 30–40 years, it comes with substantial adversely affects influencing patients’ quality of life.Certain hopes were associated in recent decades with the development of etiotropic therapy for Duchenne muscular dystrophy, aimed at restoration of the dystrophin’s function. Some of such approaches were based on the overcoming of the effect of premature stop codons in the DMD gene using aminoglycoside antibiotics, ataluren, etc. Several subsequent studies were conducted to explore the applicability of exon‑skipping approaches in the dystrophin gene, aimed at excluding exons carrying pathogenic genetic variants. The rationale for these studies was the available information about a milder course of the disease associated with a truncated but functional dystrophin. The possibility of the pathology correction by means of introduction of the exogenous functional DMD gene copy from the outside (gene replacement therapy) has been under study since the beginning of the 20th century. One of the most promising directions in recent years was the development of approaches related to genome editing, which, unlike the methods mentioned above, allows for the permanent correction of the underlying cause of genetic diseases. Some of corresponding drugs have already received approval, while others, related to gene therapy, are at the stage of clinical trials.

show abstract

Section: развитие этиотропных подходов к терапии миодистрофии дюшеннаunclassified

Stages of research and development of therapeutic approaches for Duchenne myodystrophy. Part II: etiotropic approaches

Kochergin-Nikitskiy,

Smirnikhina,

Lavrov

2024

Neuromuscular Diseases

View full text Add to dashboard Cite

show abstract

“…Liver and bone marrow transplant are available for children with OTC and adrenoleucodystrophy (Bougnères et al, 2021; Ziogas et al, 2021). Antisense oligonucleotide therapy is available for a small portion of children with Duchenne muscular dystrophy (Morkous, 2020). Gene therapy and mRNA therapy are in preclinical trials for fragile X and Rett syndrome but neither is available for clinical use (Hooper et al, 2021; Katz et al, 2012).…”

Section: Medical Carementioning

confidence: 99%

X‐Linked intellectual disability update 2022

Schwartz

Louie

Toutain

et al. 2022

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Genes that are involved in the transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination dominate the list of 21 new genes associated with X‐linked intellectual disability since the last update in 2017. The new genes were identified by sequencing of candidate genes (2), the entire X‐chromosome (2), the whole exome (15), or the whole genome (2). With these additions, 42 (21%) of the 199 named XLID syndromes and 27 (25%) of the 108 numbered nonsyndromic XLID families remain to be resolved at the molecular level. Although the pace of discovery of new XLID genes has slowed during the past 5 years, the density of genes on the X chromosome that cause intellectual disability still appears to be twice the density of intellectual disability genes on the autosomes.

show abstract

“…The type of premature stop codon did not influence treatment benefit, indicating that ataluren treatment is not affected by stop codon type. The interim results of the STRIDE Registry described above show that ataluren treatment was well tolerated and provided clinical benefits, including clinically meaningful preservation of ambulation [ 20 , 56 ].…”

Section: Main Body Of Reviewmentioning

confidence: 99%

Ataluren—Promising Therapeutic Premature Termination Codon Readthrough Frontrunner

Michorowska

2021

Pharmaceuticals

View full text Add to dashboard Cite

Around 12% of hereditary disease-causing mutations are in-frame nonsense mutations. The expression of genes containing nonsense mutations potentially leads to the production of truncated proteins with residual or virtually no function. However, the translation of transcripts containing premature stop codons resulting in full-length protein expression can be achieved using readthrough agents. Among them, only ataluren was approved in several countries to treat nonsense mutation Duchenne muscular dystrophy (DMD) patients. This review summarizes ataluren’s journey from its identification, via first in vitro activity experiments, to clinical trials in DMD, cystic fibrosis, and aniridia. Additionally, data on its pharmacokinetics and mechanism of action are presented. The range of diseases with underlying nonsense mutations is described for which ataluren therapy seems to be promising. What is more, experiments in which ataluren did not show its readthrough activity are also included, and reasons for their failures are discussed.

show abstract

Treatment with Ataluren for Duchene Muscular Dystrophy

Cited by 10 publications

References 4 publications

Stages of research and development of therapeutic approaches for Duchenne myodystrophy. Part II: etiotropic approaches

Stages of research and development of therapeutic approaches for Duchenne myodystrophy. Part II: etiotropic approaches

X‐Linked intellectual disability update 2022

Ataluren—Promising Therapeutic Premature Termination Codon Readthrough Frontrunner

Contact Info

Product

Resources

About