Patient reported quality of life and medication adherence in Fabry disease patients treated with migalastat: A prospective, multicenter study

Müntze, Jonas; Lau, Kolja; Cybulla, Markus; Brand, Eva; Cairns, Tereza; Lorenz, Lora; Üçeyler, Nurcan; Sommer, Claudia; Wanner, Christoph; Nordbeck, Peter

doi:10.1016/j.ymgme.2022.106981

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…The split between preclinical and clinical studies was equal. A summary of the included clinical studies for Fabry disease is shown in Table 2 [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 43 , 44 , 45 ]. A summary of the preclinical studies is shown in the Supplementary Material (Table S2) [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification

Keyzor,

Shohet,

Castelli

et al. 2023

Biomolecules

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The treatment landscape for lysosomal storage disorders (LSDs) is rapidly evolving. An increase in the number of preclinical and clinical studies in the last decade has demonstrated that pharmacological chaperones are a feasible alternative to enzyme replacement therapy (ERT) for individuals with LSDs. A systematic search was performed to retrieve and critically assess the evidence from preclinical and clinical applications of pharmacological chaperones in the treatment of LSDs and to elucidate the mechanisms by which they could be effective in clinical practice. Publications were screened according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines. Fifty-two articles evaluating 12 small molecules for the treatment of seven LSDs are included in this review. Overall, a substantial amount of preclinical and clinical data support the potential of pharmacological chaperones as treatments for Fabry disease, Gaucher disease, and Pompe disease. Most of the available clinical evidence evaluated migalastat for the treatment of Fabry disease. There was a lack of consistency in the terminology used to describe pharmacological chaperones in the literature. Therefore, the new small molecule chaperone (SMC) classification system is proposed to inform a standardized approach for new, emerging small molecule therapies in LSDs.

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Section: Resultsmentioning

confidence: 99%

Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification

Keyzor,

Shohet,

Castelli

et al. 2023

Biomolecules

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“…37 The iminosugar Migalastat was originally discovered as a potential drug for Fabry disease in patientderived lymphoblasts, 38,39 and it is now in clinical use for Fabry patients. 40 Our own research identified betaine (tri-methyl glycine) as a PC molecule suitable for the world-wide most common pathogenic variant in aspartylglucosaminuria (AGU). 10 This drug, also known as Cystadane ® , is approved for the treatment of homocystinuria, and our cell culture studies thus swiftly advanced into a clinical trial.…”

Section: Precision Therapies Based On Variant Typementioning

confidence: 99%

“…PC therapy has shown significant promise in many diseases, and several drugs have been repurposed as PCs, including the mucolytic substances ambroxol in Gaucher disease 32,33 and acetylcysteine in Pompe disease, 34 the antiparasitic pyrimethamine in GM2 gangliosidosis, 35,36 and the flavone diosmetin in Zellweger spectrum disorder 37 . The iminosugar Migalastat was originally discovered as a potential drug for Fabry disease in patient‐derived lymphoblasts, 38,39 and it is now in clinical use for Fabry patients 40 . Our own research identified betaine (tri‐methyl glycine) as a PC molecule suitable for the world‐wide most common pathogenic variant in aspartylglucosaminuria (AGU) 10 .…”

Section: Precision Therapies Based On Variant Typementioning

confidence: 99%

Development of precision therapies for rare inborn errors of metabolism: Functional investigations in cell culture models

Didiasova,

Banning,

Tikkanen

2023

J of Inher Metab Disea

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Due to the low number of patients, rare genetic diseases are a special challenge for the development of therapies, especially for diseases that result from numerous, patient‐specific pathogenic variants. Precision medicine makes use of various kinds of molecular information about a specific variant, so that the possibilities for an effective therapy based on the molecular features of the variants can be elucidated. The attention to personalized precision therapies has increased among scientists and clinicians, since the “single drug for all patients” approach does not allow the classification of individuals in subgroups according to the differences in the disease genotype or phenotype. This review article summarizes some approaches of personalized precision medicine that can be used for a cost‐effective and fast development of therapies, even for single patients. We have focused on specific examples on inborn errors of metabolism, with special attention on drug repurposing. Furthermore, we provide an overview of cell culture models that are suitable for precision medicine approaches.

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“…The chaperone migalastat (Galafold ® ), approved in 2016 by the European Medicines Agency (EMA), binds to the active site of α-Gal A and improves functionality of the patient’s own enzyme. However, migalastat is only effective in amenable mutations, i.e., missense mutations with a preserved residual enzyme function [ 5 , 6 ]. Other strategies for FD are currently under research, such as second generation ERT (pegunigalsidase-alfa and moss-derived α-Gal A), substrate reduction therapy (SRT), stem cell gene mRNA therapy and gene supplementation [ 3 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

Beraza-Millor¹,

Rodríguez-Castejón²,

Miranda

et al. 2023

Pharmaceutics

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Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA–golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA–golden LNP system as a promising nanomedicine to address FD by specific SRT.

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Patient reported quality of life and medication adherence in Fabry disease patients treated with migalastat: A prospective, multicenter study

Cited by 11 publications

References 37 publications

Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification

Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification

Development of precision therapies for rare inborn errors of metabolism: Functional investigations in cell culture models

Novel Golden Lipid Nanoparticles with Small Interference Ribonucleic Acid for Substrate Reduction Therapy in Fabry Disease

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