ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Merits of combination cortical, subcortical, and cerebellar injections for the treatment of Niemann-Pick disease type A.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Retention of lysosomal acid sphingomyelinase protects from Niemann-Pick Disease.Neurobiology of disease · 2025Article
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- Bi-functional IgG-lysosomal enzyme fusion proteins for brain drug delivery.Scientific reports · 2019Article
- Adeno-associated viral vector serotype 9-based gene therapy for Niemann-Pick disease type A.Science translational medicine · 2019Article
- Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation.Frontiers in neuroanatomy · 2019Review
- Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.Stem cells translational medicine · 2016Article
- Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders.Methods in molecular biology (Clifton, N.J.) · 2016Review
- Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy.Brain : a journal of neurology · 2015Article
- Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.Gene therapy · 2015Article
- Widespread and efficient transduction of spinal cord and brain following neonatal AAV injection and potential disease modifying effect in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Normalization and improvement of CNS deficits in mice with Hurler syndrome after long-term peripheral delivery of BBB-targeted iduronidase.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Gene therapy for the nervous system: challenges and new strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- Gene therapy for the neurological manifestations in lysosomal storage disorders.Journal of lipid research · 2014Review
- Adeno-associated virus serotypes 1, 8, and 9 share conserved mechanisms for anterograde and retrograde axonal transport.Human gene therapy · 2014Article
- Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction of the dog brain.Gene therapy · 2014Article
- Molecular anatomy of the gut-brain axis revealed with transgenic technologies: implications in metabolic research.Frontiers in neuroscience · 2013Article
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
Niemann-Pick disease Type A (NPA) is a neuronopathic lysosomal storage disease (LSD) caused by the loss of acid sphingomyelinase (ASM). The goals of the current study are to ascertain the levels of human ASM that are efficacious in ASM knockout (ASMKO) mice, and determine whether these levels can be attained in non-human primates (NHPs) using a multiple parenchymal injection strategy. Intracranial injections of different doses of AAV1-hASM in ASMKO mice demonstrated that only a small amount of enzyme (<0.5 mg hASM/g tissue) was sufficient to increase survival, and that increasing the amount of hASM did not enhance this survival benefit until a new threshold level of >10 mg hASM/g tissue was reached. In monkeys, injection of 12 tracts of AAV1-hASM resulted in efficacious levels of enzyme in broad regions of the brain that was aided, in part, by axonal transport of adeno-associated virus (AAV) and movement through the perivascular space. This study demonstrates that a combination cortical, subcortical, and cerebellar injection protocol could provide therapeutic levels of hASM to regions of the NHP brain that are highly affected in NPA patients. The information from this study might help design new AAV-mediated enzyme replacement protocols for NPA and other neuronopathic LSDs in future clinical trials.
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Registered trials
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.