ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Oral trehalose improves histological and behavior symptoms of mucopolysaccharidosis type II in iduronate 2-sulfatase deficient mice.Scientific reports · 2025Article
- Heparan sulfate in cerebrospinal fluid as a biomarker to assess disease severity and for treatment monitoring in patients with Mucopolysaccharidosis Type II: a position statement.Orphanet journal of rare diseases · 2024Article
- Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.International journal of molecular sciences · 2024Article
- Clinical characteristics and somatic burden of patients with mucopolysaccharidosis II with or without neurological involvement: An analysis from the Hunter Outcome Survey.Molecular genetics and metabolism reports · 2023Article
- Bringing enzymes to the proximity party.RSC chemical biology · 2023Review
- Transferrin Receptor-Targeted Iduronate-2-sulfatase Penetrates the Blood-Retinal Barrier and Improves Retinopathy in Mucopolysaccharidosis II Mice.Molecular pharmaceutics · 2023Article
- Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice.Molecular therapy. Methods & clinical development · 2023Article
- Characterization of a HIR-Fab-IDS, Novel Iduronate 2-Sulfatase Fusion Protein for the Treatment of Neuropathic Mucopolysaccharidosis Type II (Hunter Syndrome).BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Article
- Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.Molecular genetics and metabolism · 2023Article
- The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis.Biomedicines · 2023Review
- Transferrin receptor-targeting property of pabinafusp alfa facilitates its uptake by various types of human brain-derived cellsFrontiers in drug delivery · 2023Article
- Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.International journal of molecular sciences · 2022Review
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- Drug delivery for neuronopathic lysosomal storage diseases: evolving roles of the blood brain barrier and cerebrospinal fluid.Metabolic brain disease · 2022Review
- Treatment of Neuronopathic Mucopolysaccharidoses with Blood-Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
- Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice.Molecular therapy. Methods & clinical development · 2022Article
- A Preliminary Study on the Relationship between Serum Heparan Sulfate and Cancer-Related Cognitive Impairment: The Moderating Role of Oxidative Stress in Patients with Colorectal Cancer.Current oncology (Toronto, Ont.) · 2022Article
- Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: An Integrated Analysis of Preclinical and Clinical Data.International journal of molecular sciences · 2021Article
- Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome.JCI insight · 2021Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis II (MPS II), a lysosomal storage disease caused by mutations in iduronate-2-sulfatase (IDS), is characterized by a wide variety of somatic and neurologic symptoms. The currently approved intravenous enzyme replacement therapy with recombinant IDS (idursulfase) is ineffective for CNS manifestations due to its inability to cross the blood-brain barrier (BBB). Here, we demonstrate that the clearance of heparan sulfate (HS) deposited in the brain by a BBB-penetrable antibody-enzyme fusion protein prevents neurodegeneration and neurocognitive dysfunctions in MPS II mice. The fusion protein pabinafusp alfa was chronically administered intravenously to MPS II mice. The drug reduced HS and attenuated histopathological changes in the brain, as well as in peripheral tissues. The loss of spatial learning abilities was completely suppressed by pabinafusp alfa, but not by idursulfase, indicating an association between HS deposition in the brain, neurodegeneration, and CNS manifestations in these mice. Furthermore, HS concentrations in the brain and reduction thereof by pabinafusp alpha correlated with those in the cerebrospinal fluid (CSF). Thus, repeated intravenous administration of pabinafusp alfa to MPS II mice decreased HS deposition in the brain, leading to prevention of neurodegeneration and maintenance of neurocognitive function, which may be predicted from HS concentrations in CSF.
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