ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Enzyme enhancers for the treatment of Fabry and Pompe disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations.International journal of molecular sciences · 2016Pooled it
- ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies.Orphanet journal of rare diseases · 2025Review
- Impact of ER stress and the unfolded protein response on Fabry disease.EBioMedicine · 2025Review
- Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.Biomolecules · 2023Review
- Long-Term Monitoring of Cardiac Involvement under Migalastat Treatment Using Magnetic Resonance Tomography in Fabry Disease.Life (Basel, Switzerland) · 2023Article
- Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.International journal of molecular sciences · 2022Article
- Mechanistic Insight into the Mode of Action of Acid β-Glucosidase Enhancer Ambroxol.International journal of molecular sciences · 2022Article
- Quantifying lysosomal glycosidase activity within cells using bis-acetal substrates.Nature chemical biology · 2022Article
- Pharmacological Chaperone Therapy for Pompe Disease.Molecules (Basel, Switzerland) · 2021Review
- Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates.Nature communications · 2021Article
- Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease.International journal of molecular sciences · 2021Review
- Misfolding of Lysosomal α-Galactosidase a in a Fly Model and Its Alleviation by the Pharmacological Chaperone Migalastat.International journal of molecular sciences · 2020Article
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned From Gaucher and Fabry Diseases.Journal of clinical medicine · 2020Article
- Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease.The Biochemical journal · 2020Article
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease.Journal of visualized experiments : JoVE · 2017Article
- Molecular switching system using glycosylphosphatidylinositol to select cells highly expressing recombinant proteins.Scientific reports · 2017Article
- Article
- Ambroxol for the treatment of fibromyalgia: science or fiction?Journal of pain research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal storage disorders (LSD) are a group of heterogeneous diseases caused by compromised enzyme function leading to multiple organ failure. Therapeutic approaches involve enzyme replacement (ERT), which is effective for a substantial fraction of patients. However, there are still concerns about a number of issues including tissue penetrance, generation of host antibodies against the therapeutic enzyme, and financial aspects, which render this therapy suboptimal for many cases. Treatment with pharmacological chaperones (PC) was recognized as a possible alternative to ERT, because a great number of mutations do not completely abolish enzyme function, but rather trigger degradation in the endoplasmic reticulum. The theory behind PC is that they can stabilize enzymes with remaining function, avoid degradation and thereby ameliorate disease symptoms. We tested several compounds in order to identify novel small molecules that prevent premature degradation of the mutant lysosomal enzymes α-galactosidase A (for Fabry disease (FD)) and acid α-glucosidase (GAA) (for Pompe disease (PD)). We discovered that the expectorant Ambroxol when used in conjunction with known PC resulted in a significant enhancement of mutant α-galactosidase A and GAA activities. Rosiglitazone was effective on α-galactosidase A either as a monotherapy or when administered in combination with the PC 1-deoxygalactonojirimycin. We therefore propose both drugs as potential enhancers of pharmacological chaperones in FD and PD to improve current treatment strategies.
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