The central nervous system represents a major target tissue for therapeutic approach of numerous lysosomal storage disorders. Fabry disease arises from the lack or dysfunction of the lysosomal alpha-galactosidase A (GLA) enzyme, resulting in substrate accumulation and multisystemic clinical manifestations. Current enzyme replacement therapies (ERTs) face limited effectiveness due to poor enzyme biodistribution in target tissues and inability to reach the brain. We present an innovative drug delivery strategy centered on a peptide-targeted nanoliposomal formulation, designated as nanoGLA, engineered to selectively deliver a recombinant human GLA (rhGLA) to target tissues. In a Fabry mouse model, nanoGLA demonstrated improved efficacy, inducing a notable reduction in Gb3 deposits in contrast to non-nanoformulated GLA, even in the brain, highlighting the potential of the nanoGLA to address both systemic and cerebrovascular manifestations of Fabry disease. The EMA has granted the Orphan Drug Designation to this product, underscoring the potential clinical superiority of nanoGLA over authorized ERTs and encouraging to advance it toward clinical translation.
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http://dx.doi.org/10.1126/sciadv.adq4738 | DOI Listing |
Expert Opin Drug Saf
December 2024
Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Fabry disease (FD), an X-linked lysosomal disorder, is marked by a lack of alpha-galactosidase A (α-Gal A). Agalsidase beta, a recombinant form of α-Gal A, is fundamental to enzyme replacement therapy for FD but requires close monitoring for adverse events (AEs).
Research Design And Methods: This study retrospectively analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database for agalsidase beta-related AEs.
Stem Cell Res
December 2024
Department of Internal Medicine I, Division of Cardiology, University Hospital Jena, FSU Jena, Germany.
Fabry disease (FD, OMIM #301500) is a rare metabolic disorder, X-linked glycosphingolipidosis that is characterized by pathogenic mutations in the GLA (Galactosidase Alpha) gene (OMIM *300644) that result in reduced α-galactosidase A (α-GAL) activity and accumulation of globotriaosylceramide (Gb3) in tissues and organs. Peripheral blood mononuclear cells (PBMCs) were used to generate human induced pluripotent stem cells (hiPSC). UKJi004-A was produced from a healthy donor, whereas UKJi003-A was produced from a patient who had FD with GLA-mutation (IVS6-10G>A).
View Article and Find Full Text PDFJ Nephrol
December 2024
The School of Medicine, Manchester Academic Health Sciences Centre, Manchester University, Manchester, UK.
Background: Fabry disease is a rare genetic lysosomal storage disorder, whereby the accumulation of sphingolipids consequently leads to kidney structural damage and dysfunction. We explored the epidemiology of chronic kidney disease (CKD) among patients with Fabry disease at a major UK referral centre in Greater Manchester serving over 7 million people, to inform early predictors of kidney disease and possible treatment planning.
Methods: Data were sourced from the electronic records of registered participants from November 2020 to February 2022 of adults diagnosed with Fabry disease, with at least 1 year of follow-up.
J Cardiol Cases
December 2024
Department of Thoracic and Cardiovascular Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Unlabelled: A 60-year-old woman with a recent history of presumed cardiogenic cerebral infarction was referred for surgical removal of a left ventricular mass. She was diagnosed with Fabry disease eight years before. Transthoracic echocardiography showed a mobile echogenic mass in the left ventricular apex.
View Article and Find Full Text PDFZhonghua Er Ke Za Zhi
December 2024
Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou310052, China.
To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease. The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children's Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected.
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