Jul 2026· Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]· Vol 60 7, pp.
1138-1149
· 0 citations
Medicine
TL;DR
Recent advances in the molecular mechanisms, immune microenvironment involvement, and gene therapy strategies for hereditary hearing impairment are summarized, which delineates the research trajectory from gene discovery and mechanistic elucidation to therapeutic development, and discusses future translational research directions and clinical challenges.
Spinal Muscular Atrophy (SMA) is a serious autosomal recessive neuromuscular disorder. In the past few years, the rapid progresses of molecular genetics and precision medicine have greatly pushed the understanding of disease cause and the making of treatment methods for SMA. This review systematically sums up the newest advances in molecular mechanisms and accurate therapies of SMA during the time from 2024 to 2026. It highlights the regulatory roles of SMN1/SMN2 genes, non-coding RNAs, and epigenetic modifications, as well as pathophysiological alterations and disease-modifying factors induced by SMN protein deficiency. Furthermore, the clinic significances of SMN gene examination, biology markers, imaging examination, and newborn screening are all narrated in this paper. The effect and security of many accurate treatment methods, including antisense oligonucleotides, AAV-mediated gene substitution, small-molecule splicing modulators, and gene editing, are also assessed. At present, the problems that exist include the off-target effects brought by gene editing, relatively expensive treatment expenses, restricted acquisition channels, and not enough long-term follow-up observation data. Future directions include optimization of technical strategies, combination therapy, and translational application of biomarkers.
C. Yan· Theoretical and Natural Scie...· 0 citations
The study provides an integrated framework linking genetic variation to molecular dysfunction and clinical outcomes, offering valuable insights for future research and therapeutic development in pediatric neurology.
Varada Vidya Rani, Suryanarayana Reddy Kovvuri, D. Arya· Genetics and Molecular Resea...· 0 citations
This study offers the most compelling clinical evidence so far that gene replacement therapy can safely restore signi fi cant hearing in children with OTOF-related deafness, with bene fi ts lasting up to 2.5 years, setting a new standard for treating inherited sensory disorders.
B. Pattnaik, Jose-Alein Sahel· Signal Transduction and Targ...· 0 citations
This review evaluates the potential of CRISPR-based editing as a therapeutic strategy for monogenic NDDs and evaluates the limitations that must be addressed before its widespread application in human patients.
Julia Mulles· American Journal of Student...· 0 citations
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder due to pathogenic variants in the methyl CpG binding protein 2 gene (MECP2). The discovery that deficits resulting from Mecp2 loss are reversible in mice has increased interest in gene therapy as a potential cure for RTT. We have previously evaluated the efficacy of a self-complementary AAV9 vector expressing a codon-optimized version of Mecp2 (scAAV9-MCO) delivered via a systemic approach in early symptomatic Mecp2-knock-out male (KO) mice. In the present study, focused ultrasound (FUS) was used to transiently disrupt the blood-brain barrier (BBB) in a RTT mouse model, thereby facilitating enhanced AAV delivery to the central nervous system (CNS). Our findings demonstrate that scAAV9-MCO administration, when combined with FUS, significantly improves survival, body weight, respiratory function, and locomotor activity, while restoring the excitatory-inhibitory synaptic balance in hippocampal neurons in treated KO mice relative to untreated animals. Quantification of the brain infection level revealed that 20-40% of cells are Mecp2-positive in the brain of KO mice following the treatment with scAAV9-MCO and FUS. This is a significant improvement compared to prior results without FUS. The evaluation of the protein levels indicates a possible overdose of Mecp2 protein in the brain cells. Nevertheless, these results demonstrate that using FUS following systemic administration of an AAV9 vector represents a significant improvement over classical gene therapy protocol for RTT.
M. Felix, Léna Bourcin, Emilie Borloz et al.· Experimental Neurology· 0 citations
This study provides substantial evidence for the vital role of trip12 in the early stages of development, as homozygous individuals exhibited early mortality by Day 23 post-fertilization, while a substantial mortality rate was observed by Day 35 in ‘heterozygous’ mutants.
Maider Roibás-Santos, P. Suarez-Bregua, J. Rotllant et al.· Brain Communications· 0 citations
