ArticleMolecular therapy. Methods & clinical development2023
Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice.
Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- α-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A phase 1/2 trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Oral nanoparticle-encapsulated enzyme replacement therapy for mucopolysaccharidosis type I (MPS-I): a proof of concept study.Drug delivery and translational research · 2026Article
- Oral nanoparticle-encapsulated enzyme replacement therapy for mucopolysaccharidosis type I (MPS-I): a proof of concept study.Drug delivery and translational research · 2026Article
- CSF GAG non-reducing ends in MPS IH after peripheral and brain-penetrating therapies: A model comparing IV non-targeted ERT and HCT.Molecular therapy. Advances · 2026Article
- Impact of Neonatal Fc Receptor on Transferrin Receptor Antibody Fusion Protein Pharmacokinetics.Pharmaceutics · 2026Article
- Commentary: Lysosomal enzymes engineered to cross the blood-brain barrier are reshaping the therapeutic landscape of neuronopathic mucopolysaccharidoses.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing.Nature communications · 2025Article
- Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Gene therapy for ultrarare diseases: a geneticist's perspective.Journal of biomedical science · 2024Review
- Consensus-based expert recommendations on the management of MPS IVa and VI in Saudi Arabia.Orphanet journal of rare diseases · 2024Article
- An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.Science (New York, N.Y.) · 2024Article
- Molecular therapy and nucleic acid adeno-associated virus-based gene therapy delivering combinations of two growth-associated genes to MPS IVA mice.Molecular therapy. Nucleic acids · 2024Article
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- Therapeutic developments for neurodegenerative GM1 gangliosidosis.Frontiers in neuroscience · 2024Review
- An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery.bioRxiv : the preprint server for biology · 2023Article
- Transferrin Receptor-Targeted Iduronate-2-sulfatase Penetrates the Blood-Retinal Barrier and Improves Retinopathy in Mucopolysaccharidosis II Mice.Molecular pharmaceutics · 2023Article
- Crossing the gates of Babylon: Brain-penetrating enzyme replacement for lysosomal disorders.Molecular therapy. Methods & clinical development · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by dysfunction of α-L-iduronidase (IDUA), is characterized by the deposition of dermatan sulfate (DS) and heparan sulfate (HS) throughout the body, which causes several somatic and central nervous symptoms. Although enzyme-replacement therapy (ERT) is currently available to treat MPS I, it does not alleviate central nervous disorders, as it cannot penetrate the blood-brain barrier. Here we evaluate the brain delivery, efficacy, and safety of JR-171, a fusion protein comprising humanized anti-human transferrin receptor antibody Fab and IDUA, using monkeys and MPS I mice. Intravenously administered JR-171 was distributed in major organs, including the brain, and reduced DS and HS concentrations in the central nervous system and peripheral tissues. JR-171 exerted similar effects on peripheral disorders similar to conventional ERT and further reversed brain pathology in MPS I mice. We found that JR-171 improved spatial learning ability, which was seen to deteriorate in the vehicle-treated mice. Further, no safety concerns were noted in repeat-dose toxicity studies in monkeys. This study provides nonclinical evidence that JR-171 might potentially prevent and even improve disease conditions in patients with neuronopathic MPS I without serious safety concerns.
Indexed as
Identifiers
What OpenQuestion holds
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.