ArticleThe Journal of clinical investigation2021
AAV9-mediated FIG4 delivery prolongs life span in Charcot-Marie-Tooth disease type 4J mouse model.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- DDX3X overexpression in mice can cause rapid tissue-specific toxicity and mortality.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- A Head-to-Head Comparison of AAV9 Biodistribution in Mice: Routes of Administration and Age Dependence.Genes · 2026Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
- SARM1 Inhibition in Three Mouse Models of Charcot-Marie-Tooth Disease.Journal of the peripheral nervous system : JPNS · 2025Article
- Genetic Deletion of Sarm1 in Mouse Models of Three Neurological Diseases.Journal of the peripheral nervous system : JPNS · 2025Article
- Transient receptor potential vanilloid channel 2 contributes to multi-modal endoplasmic reticulum and perinuclear space dilations that can also be observed in prion-infected mice.Acta neuropathologica · 2025Article
- Expression and distribution of rAAV9 intrathecally administered in juvenile to adolescent mice.Gene therapy · 2025Article
- Developing a gene therapy for Charcot-Marie-Tooth disease: progress and challenges.Regenerative medicine · 2025Review
- Preclinical use of a clinically-relevant scAAV9/SUMF1 vector for the treatment of multiple sulfatase deficiency.Communications medicine · 2025Article
- Article
- FIG4-Related Parkinsonism and the Particularities of the I41T Mutation: A Review of the Literature.Genes · 2024Review
- Clinical Characteristics of Charcot-Marie-Tooth Disease Type 4J.Neurology · 2024Article
- Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Clinical and genetic features of patients suffering from CMT4J.Journal of neurology · 2024Article
- Altered phenotypes due to genetic interaction between the mouse phosphoinositide biosynthesis genes Fig4 and Pip4k2c.G3 (Bethesda, Md.) · 2023Article
- Clinical trials in Charcot-Marie-Tooth disorders: a retrospective and preclinical assessment.Frontiers in neurology · 2023Article
- Chloroquine corrects enlarged lysosomes in FIG4 null cells and reduces neurodegeneration in Fig4 null mice.Molecular genetics and metabolism · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
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12 authors at 3 institutions in 1 country.
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Abstract
Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive, loss-of-function mutations in FIG4, encoding a phosphoinositol(3,5)P2-phosphatase. CMT4J patients have both neuron loss and demyelination in the peripheral nervous system, with vacuolization indicative of endosome/lysosome trafficking defects. Although the disease is highly variable, the onset is often in childhood and FIG4 mutations can dramatically shorten life span. There is currently no treatment for CMT4J. Here, we present the results of preclinical studies testing a gene-therapy approach to restoring FIG4 expression. A mouse model of CMT4J, the Fig4-pale tremor (plt) allele, was dosed with a single-stranded adeno-associated virus serotype 9 (AAV9) to deliver a codon-optimized human FIG4 sequence. Untreated, Fig4plt/plt mice have a median survival of approximately 5 weeks. When treated with the AAV9-FIG4 vector at P1 or P4, mice survived at least 1 year, with largely normal gross motor performance and little sign of neuropathy by neurophysiological or histopathological evaluation. When mice were treated at P7 or P11, life span was still significantly prolonged and peripheral nerve function was improved, but rescue was less complete. No unanticipated adverse effects were observed. Therefore, AAV9-mediated delivery of FIG4 is a well-tolerated and efficacious strategy in a mouse model of CMT4J.
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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 Socratic graph.