REVIEW | doi:10.20944/preprints202301.0139.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: eteplirsen; golodirsen; viltolarsen; casimersen; WVE-N531; SRP-5051; DS-5141B; NS-089/NCNP-02; SCAAV9.U7.ACCA; ATL1102
Online: 9 January 2023 (04:18:24 CET)
Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.
REVIEW | doi:10.20944/preprints202307.1409.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: spinal and bulbar muscular atrophy; antisense therapy; oligonucleotide; splice switching; mRNA knockdown; androgen receptor; AR45
Online: 20 July 2023 (09:53:18 CEST)
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a debilitating neuromuscular disease characterized by progressive muscular weakness and neuronal degeneration, affecting 1-2 individuals per 100,000 globally. While SBMA is relatively rare, recent studies have shown a significantly higher prevalence of the disease within the indigenous population of Western Canada compared to the general population. The disease is caused by a pathogenic expansion of polyglutamine residues in the androgen receptor protein, which acts as a key transcriptional regulator for numerous genes. SBMA has no cure, and current treatments are primarily supportive and focused on symptom management. Recently, a form of precision medicine known as antisense therapy has gained traction as a promising therapeutic option for numerous neuromuscular diseases. Antisense therapy uses small synthetic oligonucleotides to confer therapeutic benefit by acting on pathogenic mRNA molecules, serving to either degrade pathogenic mRNA transcripts or helping to modulate splicing. Recent studies have explored the suitability of antisense therapy for the treatment of SBMA, primarily focused on antisense-mediated mRNA knockdown approaches. Advancements in understanding the pathogenesis of SBMA and the development of targeted therapies offer hope for improved quality of life for individuals affected by this debilitating condition. Continued research is essential to optimize these genetic approaches, ensuring their safety and efficacy.