ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- 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
- The Ighmbp2-R604X mouse presents with the most severe SMARD1 clinical symptoms resulting in failure to thrive, respiratory and feeding deficits, aspiration and severe axon and muscle pathology.Neurobiology of disease · 2025Article
- Spatiotemporal deciphering of dynamic the FUS interactome during liquid-liquid phase separation in living cells.Nature communications · 2025Article
- 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
- Developing a gene therapy for Charcot-Marie-Tooth disease: progress and challenges.Regenerative medicine · 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
- IGHMBP2 deletion suppresses translation and activates the integrated stress response.Life science alliance · 2024Article
- Article
- Disease Mechanisms and Therapeutic Approaches in SMARD1-Insights from Animal Models and Cell Models.Biomedicines · 2024Review
- The contribution and therapeutic implications of IGHMBP2 mutations on IGHMBP2 biochemical activity and ABT1 association.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Case report: Heterozygous variation in the IGHMBP2 gene leading to spinal muscular atrophy with respiratory distress type 1.Frontiers in neurology · 2024Article
- IGHMBP2 deletion suppresses translation and activates the integrated stress response.bioRxiv : the preprint server for biology · 2023Article
- Clinically relevant mouse models of Charcot-Marie-Tooth type 2S.Human molecular genetics · 2023Article
- ABT1 modifies SMARD1 pathology via interactions with IGHMBP2 and stimulation of ATPase and helicase activity.JCI insight · 2023Article
- Clinical trials in Charcot-Marie-Tooth disorders: a retrospective and preclinical assessment.Frontiers in neurology · 2023Article
- The Ighmbp2D564N mouse model is the first SMARD1 model to demonstrate respiratory defects.Human molecular genetics · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease occurring during childhood. The gene responsible for disease development is a ubiquitously expressed protein, IGHMBP2. Mutations in IGHMBP2 result in the loss of α-motor neurons leading to muscle atrophy in the distal limbs accompanied by respiratory complications. Although genetically and clinically distinct, proximal SMA is also caused by the loss of a ubiquitously expressed gene (SMN). Significant preclinical success has been achieved in proximal SMA using viral-based gene replacement strategies. We leveraged the technologies employed in SMA to demonstrate gene replacement efficacy in an SMARD1 animal model. Intracerebroventricular (ICV) injection of single-stranded AAV9 expressing the full-length cDNA of IGHMBP2 in a low dose led to a significant level of rescue in treated SMARD1 animals. Consistent with drastically increased survival, weight gain, and strength, the rescued animals demonstrated a significant improvement in muscle, NMJ, motor neurons, and axonal pathology. In addition, increased levels of IGHMBP2 in lumbar motor neurons verified the efficacy of the virus to transduce the target tissues. Our results indicate that AAV9-based gene replacement is a viable strategy for SMARD1, although dosing effects and potential negative impacts of high dose and ICV injection should be thoroughly investigated.
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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.