ArticleEBioMedicine2018
The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment.Journal of inherited metabolic disease · 2021Trial
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Article
- Allosteric Modulation of GCase Enhances Lysosomal Activity and Reduces ER Stress in GCase-Related Disorders.International journal of molecular sciences · 2025Article
- Amplifying the Heat Shock Response Ameliorates ALS and FTD Pathology in Mouse and Human Models.Molecular neurobiology · 2023Article
- Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.Biomolecules · 2023Review
- Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial.Brain : a journal of neurology · 2023Article
- Potential roles of the endoplasmic reticulum stress pathway in amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2023Review
- Quantitative Comparison of HSF1 Activators.Molecular biotechnology · 2022Article
- Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.International journal of molecular sciences · 2022Article
- Review
- Gaucher disease - more than just a rare lipid storage disease.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Genetic variations inFrontiers in neurology · 2022Review
- A micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor-American journal of cancer research · 2022Article
- Loss of Function of Mutant IDS Due to Endoplasmic Reticulum-Associated Degradation: New Therapeutic Opportunities for Mucopolysaccharidosis Type II.International journal of molecular sciences · 2021Review
- The rapidly evolving view of lysosomal storage diseases.EMBO molecular medicine · 2021Review
- Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA-associated Parkinson's disease and their targeted therapeutic approaches: a comprehensive review.Translational neurodegeneration · 2021Review
- Recent advances in understanding the role of proteostasis.Faculty reviews · 2021Review
- A patient with Gaucher disease and plasma cell dyscrasia: bidirectional impact.Hematology. American Society of Hematology. Education Program · 2020Review
- The natural history of type 2 Gaucher disease in the 21st century: A retrospective study.Neurology · 2020Article
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins are well known cytoprotective molecules with functions in protein homeostasis and lysosomal function and their manipulation has been suggested as a potential therapeutic strategy for GD. The investigational drug arimoclomol, which is in phase II/III clinical trials, is a well-characterized HSP amplifier and has been extensively clinically tested. Importantly, arimoclomol efficiently crosses the blood-brain-barrier presenting an opportunity to target the neurological manifestations of GD, which remains without a disease-modifying therapy.
methodsWe used a range of biological and biochemical in vitro assays to assess the effect of arimoclomol on GCase activity in ex vivo systems of primary fibroblasts and neuronal-like cells from GD patients.
findingsWe found that arimoclomol induced relevant HSPs such as ER-resident HSP70 (BiP) and enhanced the folding, maturation, activity, and correct cellular localization of mutated GCase across several genotypes including the common L444P and N370S mutations in primary cells from GD patients. These effects where recapitulated in a human neuronal model of GD obtained by differentiation of multipotent adult stem cells.
interpretationThese data demonstrate the potential of HSP-targeting therapies in GCase-deficiencies and strongly support the clinical development of arimoclomol as a potential therapeutic option for the neuronopathic forms of GD.
fundingThe research was funded by Orphazyme A/S, Copenhagen, Denmark.
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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.