ArticleScience advances2015
Gene therapy rescues disease phenotype in a spinal muscular atrophy with respiratory distress type 1 (SMARD1) mouse model.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- A class of deep intronicmedRxiv : the preprint server for health sciences · 2026Article
- AAV9 gene therapy optimization for SMARD1/CMT2S: safety and long-term efficacy comparison of two vectors in a SMARD1 preclinical model.Journal of biomedical science · 2026Article
- Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Developing a gene therapy for Charcot-Marie-Tooth disease: progress and challenges.Regenerative medicine · 2025Review
- A dose escalation and safety study of AAVrh10-mediated Schwann cell-targeted gene therapy for CMT1X.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Precision therapeutic targets for HPV-positive cancers: an overview and new insights.Infectious agents and cancer · 2025Review
- Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.Molecular therapy. Nucleic acids · 2025Article
- Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.Human molecular genetics · 2025Article
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- Disease Mechanisms and Therapeutic Approaches in SMARD1-Insights from Animal Models and Cell Models.Biomedicines · 2024Review
- Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot-Marie-Tooth type 2A.Cellular and molecular life sciences : CMLS · 2023Article
- In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders.Biology · 2023Article
- Clinically relevant mouse models of Charcot-Marie-Tooth type 2S.Human molecular genetics · 2023Article
- Gene therapy in neuromuscular disorders.Arquivos de neuro-psiquiatria · 2022Review
- The Ighmbp2D564N mouse model is the first SMARD1 model to demonstrate respiratory defects.Human molecular genetics · 2022Article
- Defining the optimal dose and therapeutic window in SMA with respiratory distress type I model mice, FVB/NJ-Molecular therapy. Methods & clinical development · 2021Article
- Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies.International journal of molecular sciences · 2021Review
- Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF.Pediatric pulmonology · 2021Review
- Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).Cellular and molecular life sciences : CMLS · 2020Review
- A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease affecting children. It is caused by mutations in the IGHMBP2 gene (11q13) and presently has no cure. Recently, adeno-associated virus serotype 9 (AAV9)-mediated gene therapy has been shown to rescue the phenotype of animal models of another lower motor neuron disorder, spinal muscular atrophy 5q, and a clinical trial with this strategy is ongoing. We report rescue of the disease phenotype in a SMARD1 mouse model after therapeutic delivery via systemic injection of an AAV9 construct encoding the wild-type IGHMBP2 to replace the defective gene. AAV9-IGHMBP2 administration restored protein levels and rescued motor function, neuromuscular physiology, and life span (450% increase), ameliorating pathological features in the central nervous system, muscles, and heart. To test this strategy in a human model, we transferred wild-type IGHMBP2 into human SMARD1-induced pluripotent stem cell-derived motor neurons; these cells exhibited increased survival and axonal length in long-term culture. Our data support the translational potential of AAV-mediated gene therapies for SMARD1, opening the door for AAV9-mediated therapy in human clinical trials.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.