ArticleExperimental neurology2009
Intracerebroventricular infusion of acid sphingomyelinase corrects CNS manifestations in a mouse model of Niemann-Pick A disease.
Article in Experimental neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 74 citations in OpenAlex.
- AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition and Lipid Droplets Accumulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Retention of lysosomal acid sphingomyelinase protects from Niemann-Pick Disease.Neurobiology of disease · 2025Article
- Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.Human molecular genetics · 2025Article
- The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review.Biomolecules · 2024Review
- The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency.Genetics in medicine open · 2024Review
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery.Molecular therapy. Methods & clinical development · 2022Article
- Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Sphingolipids as Regulators of Neuro-Inflammation and NADPH Oxidase 2.Neuromolecular medicine · 2021Review
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- 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
- Widespread brain distribution and activity following i.c.v. infusion of anti-β-secretase (BACE1) in nonhuman primates.British journal of pharmacology · 2017Article
- Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA.Journal of inherited metabolic disease · 2017Article
- Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a Simple Problem.Pediatric endocrinology reviews : PER · 2016Review
- Clinical Improvement of Alpha-mannosidosis Cat Following a Single Cisterna Magna Infusion of AAV1.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Continual Low-Dose Infusion of Sulfamidase Is Superior to Intermittent High-Dose Delivery in Ameliorating Neuropathology in the MPS IIIA Mouse Brain.JIMD reports · 2016Article
- Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain.Journal of inherited metabolic disease · 2015Article
- Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.PloS one · 2015Article
- Gene therapy for the neurological manifestations in lysosomal storage disorders.Journal of lipid research · 2014Review
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12 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick A (NPA) disease is a lysosomal storage disorder (LSD) caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously, we showed that the storage pathology in the ASM knockout (ASMKO) mouse brain could be corrected by intracerebral injections of cell, gene and protein based therapies. However, except for instances where distal areas were targeted with viral vectors, correction of lysosomal storage pathology was typically limited to a region within a few millimeters from the injection site. As NPA is a global neurometabolic disease, the development of delivery strategies that maximize the distribution of the enzyme throughout the CNS is likely necessary to arrest or delay progression of the disease. To address this challenge, we evaluated the effectiveness of intracerebroventricular (ICV) delivery of recombinant human ASM into ASMKO mice. Our findings showed that ICV delivery of the enzyme led to widespread distribution of the hydrolase throughout the CNS. Moreover, a significant reduction in lysosomal accumulation of sphingomyelin was observed throughout the brain and also within the spinal cord and viscera. Importantly, we demonstrated that repeated ICV infusions of ASM were effective at improving the disease phenotype in the ASMKO mouse as indicated by a partial alleviation of the motor abnormalities. These findings support the continued exploration of ICV delivery of recombinant lysosomal enzymes as a therapeutic modality for LSDs such as NPA that manifests substrate accumulation within the CNS.
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