An expert consensus on practical clinical recommendations and guidance for patients with classic Fabry disease

Molecular Genetics and Metabolism, Journal Year: 2022, Volume and Issue: 137(1-2), P. 49 - 61

Published: July 27, 2022

Fabry disease is an X-linked inherited lysosomal disorder that causes accumulation of glycosphingolipids in body fluids and tissues, leading to progressive organ damage reduced life expectancy. It can affect both males females be classified into classic or later-onset phenotypes. In disease, α-galactosidase A (α-Gal A) activity absent severely manifestations have early onset multiple organs. contrast, patients residual α-Gal clinical features are primarily confined the heart. Individualized therapeutic goals required due varying phenotypes patient characteristics, wide spectrum severity. An international group expert physicians convened discuss develop practical recommendations for disease- organ-specific based on consensus evidence identified through a structured literature review. Biomarkers reflecting involvement various organs adult with discussed provided. These should support establishment individualized approaches management by considering identification, diagnosis, initiation disease-specific therapies before significant involvement, as well routine monitoring, reduce morbidity, optimize care, improve health-related quality life.

Language: Английский

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Chaperone Therapy in Fabry Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1887 - 1887

Published: Feb. 8, 2022

Fabry disease is an X-linked lysosomal multisystem storage disorder induced by a mutation in the alpha-galactosidase A (GLA) gene. Reduced activity or deficiency of (AGAL) leads to escalating intracellular globotriaosylceramide (GL-3) numerous organs, including kidneys, heart and nerve system. The established treatment for 20 years intravenous enzyme replacement therapy. Lately, oral chaperone therapy was introduced therapeutic alternative patients with amenable mutations. Early starting essential long-term improvement. This review describes disease.

Language: Английский

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Current and Emerging Therapies for Lysosomal Storage Disorders

Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Language: Английский

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An expert consensus on the recommendations for the use of biomarkers in Fabry disease

Molecular Genetics and Metabolism, Journal Year: 2023, Volume and Issue: 139(2), P. 107585 - 107585

Published: April 18, 2023

Fabry disease is an X-linked lysosomal storage disorder caused by the accumulation of glycosphingolipids in various tissues and body fluids, leading to progressive organ damage life-threatening complications. Phenotypic classification based on progression severity can be used predict outcomes. Patients with a classic phenotype have little no residual α-Gal A activity widespread involvement, whereas patients later-onset limited single organ, often heart. Diagnosis monitoring should therefore individualized, biomarkers are available support this. Disease-specific useful diagnosis disease; non-disease-specific may assess damage. For most it challenging prove they translate differences risk clinical events associated disease. Therefore, careful treatment outcomes collection prospective data needed. As we deepen our understanding disease, important regularly re-evaluate appraise published evidence relating biomarkers. In this article, present results literature review between February 2017 July 2020 impact disease-specific provide expert consensus recommendations for use those

Language: Английский

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A review and recommendations for oral chaperone therapy in adult patients with Fabry disease

Orphanet Journal of Rare Diseases, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 18, 2024

Abstract Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding enzyme α-galactosidase A. FD-affected patients represent highly variable clinical course with first symptoms already appearing young age. The causes progressive multiple organ dysfunction mostly heart, kidneys nervous system, eventually leading to premature death. Disease-specific management of FD includes replacement therapy agalsidase α β or pharmacological oral chaperone migalastat. Migalastat low-molecular-mass iminosugar, that reversibly binds active site amenable variants, stabilizing their molecular structure improving trafficking lysosome. was approved EU 2016 an effective estimated 35–50% all GLA variants. This position statement comprehensive review Central Eastern Europe current role migalastat treatment FD. provides overview pharmacology summarizes evidence from trial program regarding safety efficacy drug its effects on organs typically involved paper also practical guide for clinicians optimal selection who will benefit treatment, recommendations diagnostic tests use tools identify mutations. Areas future research have been identified.

Language: Английский

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Fabry Disease: Current and Novel Therapeutic Strategies. A Narrative Review

Current Neuropharmacology, Journal Year: 2022, Volume and Issue: 21(3), P. 440 - 456

Published: June 2, 2022

Fabry disease (FD) is an inherited lysosomal storage disorder, leading to multisystemic manifestations and causing significant morbidity mortality.The aim of this narrative review present the current novel therapeutic strategies in FD, including symptomatic specific treatment options.A systematic literature search was conducted identify relevant studies, completed ongoing randomized-controlled clinical trials (RCTs), prospective or retrospective cohort case series reports that provided data regarding FD treatment.A multidisciplinary recommended for patients, personalized according their severity. During last two decades, FD-specific treatments, enzyme-replacement-therapies (agalsidase alfa agalsidase beta) chaperone with migalastat have been approved use allowed symptoms' stabilization even burden reduction. More agents are currently under investigation. Substrate reduction therapies, lucerastat venglustat, shown promising results RCTs may be used either as monotherapy complementary therapy established enzymereplacement- therapies. stable enzyme-replacement-therapy molecules associated less adverse events lower likelihood neutralizing antibodies formation also developed. Ex-vivo in-vivo gene being tested animal models pilot human trials, preliminary showing a favorable safety efficacy profile.The landscape appears actively expanding more options expected become available near future, allowing approach patients.

Language: Английский

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Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes

Journal of Medical Genetics, Journal Year: 2022, Volume and Issue: 60(7), P. 722 - 731

Published: Dec. 21, 2022

Background Fabry disease is a rare, multisystemic disorder caused by GLA gene variants that lead to alpha galactosidase A deficiency, resulting in accumulation of glycosphingolipids and cellular dysfunction. Fabry-associated clinical events (FACEs) cause significant morbidity mortality, yet the long-term effect therapies on FACE incidence remains unclear. Methods This posthoc analysis evaluated FACEs (as composite outcome separately for renal, cardiac cerebrovascular events) 97 enzyme replacement therapy (ERT)-naïve ERT-experienced adults with amenable who were treated migalastat up 8.6 years (median: 5 years) Phase III trials migalastat. Associations between baseline characteristics also evaluated. Results During treatment, 17 patients (17.5%) experienced 22 there no deaths. The rate was 48.3 per 1000 patient-years overall. Numerically higher rates observed men versus women, aged >40 younger patients, ERT-naïve classic phenotype women all other phenotypes. There statistically difference time first when analysed patient sex, phenotype, prior treatment status or age. Lower estimated glomerular filtration (eGFR) associated an increased risk across populations. Conclusions overall during compared favourably historic reports involving ERT. eGFR predictor FACEs.

Language: Английский

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

Biomolecules, Journal Year: 2023, Volume and Issue: 13(8), P. 1227 - 1227

Published: Aug. 7, 2023

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

Language: Английский

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Fabry Disease: Switch from Enzyme Replacement Therapy to Oral Chaperone Migalastat: What Do We Know Today?

Healthcare, Journal Year: 2023, Volume and Issue: 11(4), P. 449 - 449

Published: Feb. 4, 2023

Fabry disease is a lysosomal storage disorder caused by the deficiency of α-galactosidase-A enzyme. The result progressive accumulation complex glycosphingolipids and cellular dysfunction. Cardiac, renal, neurological involvement significantly reduces life expectancy. Currently, there increasing evidence that clinical response to treatment improves with early timely initiation. Until few years ago, options for were limited enzyme replacement therapy agalsidase alfa or beta administered intravenous infusion every 2 weeks. Migalastat (Galafold®) an oral pharmacological chaperone increases activity "amenable" mutations. safety efficacy migalastat supported in phase III FACETS ATTRACT studies, compared available therapies, showing reduction left ventricular mass, stabilization kidney function plasma Lyso-Gb3. Similar results confirmed subsequent extension publications, both patients who started as their first previously on switched migalastat. In this review we describe switching from mutations, referring publications date.

Language: Английский

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Inflammation, Oxidative Stress, and Endothelial Dysfunction in the Pathogenesis of Vascular Damage: Unraveling Novel Cardiovascular Risk Factors in Fabry Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8273 - 8273

Published: July 29, 2024

Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A

Language: Английский

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