Article
Biotechnology & Applied Microbiology
Silvere Pagant, Marshall W. Huston, Luciana Moreira, Lin Gan, Susan St Martin, Scott Sproul, Michael C. Holmes, Kathleen Meyer, Thomas Wechsler, Robert J. Desnick, Makiko Yasuda
Summary: The study demonstrates the potential of liver-targeted in vivo genome editing using zinc-finger nucleases to insert human alpha-galactosidase A cDNA in Fabry mice, leading to increased enzyme activity and normalization of substrate levels in key tissues. The optimized strategy achieved significant therapeutic effects with minimal hepatocyte editing, suggesting that this approach could serve as an effective one-time therapy for Fabry disease.
Article
Biochemistry & Molecular Biology
Ulrich Jehn, Samet Bayraktar, Solvey Pollmann, Veerle Van Marck, Thomas Weide, Hermann Pavenstadt, Eva Brand, Malte Lenders
Summary: Fabry disease (FD) is caused by mutations in the GLA gene, leading to cellular accumulation of globotriaosylcermide and dysregulation of various cellular pathways. Imbalanced protein expression was identified in different cell types, indicating the need for more comprehensive therapies to reverse these disturbances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Transplantation
Malte Lenders, Eva Brand
Summary: Fabry disease is a rare genetic disorder caused by mutations in the GLA gene, leading to alpha-galactosidase A deficiency and resulting in severe complications such as renal failure, cardiomyopathy, and cerebrovascular events. Current treatment options include enzyme replacement therapies and oral pharmacological chaperones, but adverse reactions like infusion-associated reactions and anti-drug antibodies formation may limit efficacy.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2021)
Article
Medicine, Research & Experimental
Fabian Braun, Ahmed Abed, Dominik Sellung, Manuel Rogg, Mathias Woidy, Oysten Eikrem, Nicola Wanner, Jessica Gambardella, Sandra D. Laufer, Fabian Haas, Milagros N. Wong, Bernhard Dumoulin, Paula Rischke, Anne Muehlig, Wiebke Sachs, Katharina von Cossel, Kristina Schulz, Nicole Muschol, Soeren W. Gersting, Ania C. Muntau, Oliver Kretz, Oliver Hahn, Markus M. Rinschen, Michael Mauer, Tillmann Bork, Florian Grahammer, Wei Liang, Thorsten Eierhoff, Winfried Roemer, Arne Hansen, Catherine Meyer-Schwesinger, Guido Iaccarino, Camilla Tondel, Hans-Peter Marti, Behzad Najafian, Victor G. Puelles, Christoph Schell, Tobias B. Huber
Summary: Current therapies for Fabry disease, such as enzyme replacement therapy (ERT), aim to reduce globotriaosylceramide (Gb3) accumulation, but their effect on reversing end-organ damage remains unclear. This study showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Modulating α-synuclein (SNCA) showed more beneficial effects in improving lysosomal structure and function in Fabry podocytes compared to ERT. This research highlights the importance of considering SNCA modulation as a potential intervention for Fabry nephropathy.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Franziska Alfen, Elena Putscher, Michael Hecker, Uwe Klaus Zettl, Andreas Hermann, Jan Lukas
Summary: Fabry disease is a rare genetic disorder caused by mutations in the GLA gene. This study investigated the impact of these mutations on splicing behavior and found that abnormal splicing can lead to reduced enzyme activity and affect treatment options. Experimental analysis confirmed alternative splicing events for specific mutations, highlighting the importance of splicing phenotype analysis in studying exonic GLA gene mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Arnold E. Stuetz, Martin Thonhofer, Patrick Weber, Andreas Wolfsgruber, Tanja M. Wrodnigg
Summary: The article presents a brief survey on selected beta-galactosidase inhibitors as potential pharmacological chaperones for G(M1)-gangliosidosis and Morquio B associated mutants of human lysosomal beta-galactosidase, highlighting recent developments in this specific area of lysosomal storage disorders and orphan diseases.
Article
Medicine, General & Internal
Daniel G. Bichet, Robert J. Hopkin, Patricio Aguiar, Sridhar R. Allam, Yin-Hsiu Chien, Roberto Giugliani, Staci Kallish, Sabina Kineen, Olivier Lidove, Dau-Ming Niu, Iacopo Olivotto, Juan Politei, Paul Rakoski, Roser Torra, Camilla Tondel, Derralynn A. Hughes
Summary: This study aims to provide consensus recommendations for the treatment and monitoring of Fabry disease patients receiving migalastat. A modified Delphi process was conducted and consensus was reached on treatment decisions and monitoring. The expert panel agreed on 49 out of 54 statements.
FRONTIERS IN MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Andrea Modrego, Marilla Amaranto, Agustina Godino, Rosa Mendoza, Jose Luis Barra, Jose Luis Corchero
Summary: Fabry disease is a lysosomal storage disease caused by mutations in the GLA gene, leading to the accumulation of glycosphingolipids. Current treatments include enzyme replacement therapy and pharmacological chaperone therapy, but new strategies such as gene therapy and substrate reduction therapy are being extensively studied. Mutants of GLA with improved enzymatic activity may offer advantages over current therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Health Care Sciences & Services
Fernando Perretta, Sebastian Jaurretche
Summary: Fabry disease is a genetic disorder caused by a specific enzyme deficiency, resulting in the accumulation of complex substances and dysfunction in various organs. Early and timely treatment can improve clinical response. Migalastat has shown safety and efficacy in switching patients from enzyme replacement therapy, reducing ventricular mass and stabilizing kidney function.
Article
Nanoscience & Nanotechnology
Judit Tomsen-Melero, Solene Passemard, Natalia Garcia-Aranda, Zamira Vanessa Diaz-Riascos, Ramon Gonzalez-Rioja, Jannik Nedergaard Pedersen, Jeppe Lyngso, Josep Merlo-Mas, Edgar Cristobal-Lecina, Jose Luis Corchero, Daniel Pulido, Patricia Camara-Sanchez, Irina Portnaya, Inbal Ionita, Simo Schwartz Jr, Jaume Veciana, Santi Sala, Miriam Royo, Alba Cordoba, Dganit Danino, Jan Skov Pedersen, Elisabet Gonzalez-Mira, Ibane Abasolo, Nora Ventosa
Summary: The incorporation of cationic miristalkonium chloride (MKC) surfactant into RGD nanovesicles has been shown to improve loading capacity and colloidal stability, enhancing the protection and delivery of the enzyme. Using MKC in two different nanosystems increases the stability of enzyme loading, with low concentrations of MKC in hybrid liposomes stabilizing the enzyme without compromising its activity. Hybrid liposomes also show improved efficacy in cell cultures and a good safety profile, ensuring their potential for future preclinical and clinical development.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Methus Klaewkla, Jittithorn Prousoontorn, Thanapon Charoenwongpaiboon
Summary: This study investigated the effect of mutation on the secondary structure, structural energy, and galactose affinity of alpha-Gal A using molecular dynamics simulations and free energy calculations. The results showed that the A143T mutation induced the formation of unusual H-bonds, resulting in changes in secondary structure and binding affinities towards galactose. The identified molecular binding mechanism could be helpful for the optimization and design of new galactose analogs as pharmacological chaperones against Fabry disease.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pedro Besada, Maria Gallardo-Gomez, Tania Perez-Marquez, Lucia Patino-alvarez, Sergio Pantano, Carlos Silva-Lopez, Carmen Teran, Ana Arevalo-Gomez, Aurora Ruz-Zafra, Julian Fernandez-Martin, Saida Ortolano
Summary: The study demonstrated that PBX compounds are safe and effective in stabilizing alpha-Galactosidase A in disease-relevant cellular models, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations that affect the folding of alpha-Galactosidase A, even for GLA variants that are not amenable to treatment with Migalastat.
Article
Pharmacology & Pharmacy
Julen Rodriguez-Castejon, Ana Alarcia-Lacalle, Itziar Gomez-Aguado, Monica Vicente-Pascual, Maria Angeles Solinis Aspiazu, Ana del Pozo-Rodriguez, Alicia Rodriguez-Gascon
Summary: Fabry disease is a monogenic disorder that can be treated with gene therapy. Research has shown that a non-viral vector based on solid lipid nanoparticles can effectively increase enzyme activity in an FD mouse model, demonstrating therapeutic potential.
Review
Biochemistry & Molecular Biology
Ken Kok, Kimberley C. Zwiers, Rolf G. Boot, Hermen S. Overkleeft, Johannes M. F. G. Aerts, Marta Artola
Summary: Fabry disease is a lysosomal storage disorder characterized by the deficiency of alpha-galactosidase A and the accumulation of toxic metabolites. There is currently no cure for Fabry disease, but treatment options include enzyme replacement therapy, pharmacological chaperone therapy, substrate reduction therapy, and gene/RNA therapy.
Article
Microbiology
Samuel Berhanu, Takuya Ueda, Jean-Herve Alix
Summary: This study reveals the difference in alpha-complementation between pUC18 and pUC19 plasmid vectors, with pUC18 requiring the assistance of the DnaK/DnaJ/GrpE chaperone system and pUC19 being more efficient without it. This observation can be utilized in screening for DnaK inhibitors and understanding the DnaK-mediated protein quality control mechanism.
JOURNAL OF BASIC MICROBIOLOGY
(2022)