Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases

Abstract

Neuromuscular diseases (NMDs) belong to a class of functional impairments that cause dysfunctions of the motor neuron-muscle functional axis components. Inherited monogenic neuromuscular disorders encompass both muscular dystrophies and motor neuron diseases. Understanding of their causative genetic defects and pathological genetic mechanisms has led to the unprecedented clinical translation of genetic therapies. Challenged by a broad range of gene defect types, researchers have developed different approaches to tackle mutations by hijacking the cellular gene expression machinery to minimize the mutational damage and produce the functional target proteins. Such manipulations may be directed to any point of the gene expression axis, such as classical gene augmentation, modulating premature termination codon ribosomal bypass, splicing modification of pre-mRNA, etc. With the soar of the CRISPR-based gene editing systems, researchers now gravitate toward genome surgery in tackling NMDs by directly correcting the mutational defects at the genome level and expanding the scope of targetable NMDs. In this article, we will review the current development of gene therapy and focus on NMDs that are available in published reports, including Duchenne Muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked myotubular myopathy (XLMTM), Spinal Muscular Atrophy (SMA), and Limb-girdle muscular dystrophy Type 2C (LGMD2C).

A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene–disease relationships

“…The male infertility field is currently catching up with other fields/disease types with a strong genetic component, such as intellectual disability, neuromuscular disorders and hereditary hearing impairments ( Chiu et al , 2020 ; Markitantova and Simirskii, 2020 ; Whatley et al , 2020 ). The rapid uptake of NGS technologies in the male infertility research field over the past 5–10 years, as well as the development of international consortia to collect and characterise clinical cohorts, is aiding in the transition of findings into clinical practice.…”

Innovative Therapeutic Approaches for Duchenne Muscular Dystrophy

“…Gene replacement is an ideal method for treating monogenic, autosomal, or X-linked recessive diseases like DMD or beta-thalassemia, where the gene of interest can fit into the delivery vector [70,71].…”

Editorial for Special Issue “Genetic Basis and Epidemiology of Myopathies”

“…The review highlights both differences and commonalities across the animal models, which contributes to better understanding the models’ advantages and deficiencies. The fifth paper, titled “Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases”, by [ 5 ] reviews studies that have focused on next-generation sequencing and genetic tools within the context of gene therapies for neuromuscular diseases. The review highlights both the interaction between mutations and the severity of the clinical phenotype, and the phenotype–genotype associations in neuromuscular diseases.…”