ArticleProceedings of the National Academy of Sciences of the United States of America2003
Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 263 citations in OpenAlex.
- Development of Small-Molecule Allosteric Modulators of Beta-Galactosidase (β-Gal) for the Treatment of GM1 Gangliosidosis and Morquio B.International journal of molecular sciences · 2026Article
- Enzymatic and synthetic regulation of polypeptide folding.Chemical science · 2024Review
- Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.Biomolecules · 2023Review
- Ganglioside GM1 and the Central Nervous System.International journal of molecular sciences · 2023Review
- Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.The Journal of experimental medicine · 2022Article
- Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis.Molecules (Basel, Switzerland) · 2022Article
- Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Design and synthesis of biologically active carbaglycosylamines: From glycosidase inhibitors to pharmacological chaperones.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Sphingolipid lysosomal storage diseases: from bench to bedside.Lipids in health and disease · 2021Review
- GM1 Gangliosidosis: Mechanisms and Management.The application of clinical genetics · 2021Review
- GM1 Gangliosidosis-A Mini-Review.Frontiers in genetics · 2021Review
- Synthesis of "Molecules (Basel, Switzerland) · 2020Article
- Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes andMolecules (Basel, Switzerland) · 2020Article
- Lysosomal storage diseases: current therapies and future alternatives.Journal of molecular medicine (Berlin, Germany) · 2020Review
- The pharmacological chaperone N-n-butyl-deoxygalactonojirimycin enhances β-galactosidase processing and activity in fibroblasts of a patient with infantile GM1-gangliosidosis.Human genetics · 2020Article
- Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment.International journal of molecular sciences · 2020Review
- Morquio-B disease: Clinical and genetic characteristics of a distinctJIMD reports · 2020Article
- Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses.International journal of molecular sciences · 2019Review
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
We synthesized a galactose derivative, N-octyl-4-epi-beta-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, beta-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal beta-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with beta-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
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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.