The Experts below are selected from a list of 1371 Experts worldwide ranked by ideXlab platform
Ellen Van Beusekom - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-l-Ribitol Pyrophosphorylase A Muscular Dystrophy
Clinical chemistry, 2019Co-Authors: Walinka Van Tol, Monique Van Scherpenzeel, Mohammad Alsady, Moniek Riemersma, Esther Hermans, Else Kragt, Giorgio Tasca, Erik-jan Kamsteeg, Maartje Pennings, Ellen Van BeusekomAbstract:BACKGROUND: Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for Cytidine Diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. METHODS: An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. RESULTS: CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker–Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. CONCLUSIONS: Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.
Zhenfeng Liu - One of the best experts on this subject based on the ideXlab platform.
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Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis
Nature communications, 2014Co-Authors: Xiuying Liu, Yan Yin, Zhenfeng LiuAbstract:Cytidine-Diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al. report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.
Walinka Van Tol - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-l-Ribitol Pyrophosphorylase A Muscular Dystrophy
Clinical chemistry, 2019Co-Authors: Walinka Van Tol, Monique Van Scherpenzeel, Mohammad Alsady, Moniek Riemersma, Esther Hermans, Else Kragt, Giorgio Tasca, Erik-jan Kamsteeg, Maartje Pennings, Ellen Van BeusekomAbstract:BACKGROUND: Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for Cytidine Diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. METHODS: An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. RESULTS: CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker–Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. CONCLUSIONS: Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.
Xiuying Liu - One of the best experts on this subject based on the ideXlab platform.
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Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis
Nature communications, 2014Co-Authors: Xiuying Liu, Yan Yin, Zhenfeng LiuAbstract:Cytidine-Diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al. report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.
Erik-jan Kamsteeg - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-l-Ribitol Pyrophosphorylase A Muscular Dystrophy
Clinical chemistry, 2019Co-Authors: Walinka Van Tol, Monique Van Scherpenzeel, Mohammad Alsady, Moniek Riemersma, Esther Hermans, Else Kragt, Giorgio Tasca, Erik-jan Kamsteeg, Maartje Pennings, Ellen Van BeusekomAbstract:BACKGROUND: Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for Cytidine Diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. METHODS: An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. RESULTS: CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker–Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. CONCLUSIONS: Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.
