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Stroke and Transient Ischemic Attacks of the Brain and Eye
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by GLA gene mutations that result in α-galactosidase deficiency and subsequent accumulation of globotriaosylceramide in various organs (Table 12.23). Progressive accumulation of globotriaosylceramide in endothelial and vascular smooth muscle cells causes progressive stenosis and occlusion of small arterial vessels. Furthermore, the large vessels dilate, resulting in dolichoectatic changes and flow stagnation, particularly in the posterior circulation (e.g. basilar artery), increasing the risk of artery-to-artery embolism and vessel thrombosis. Hence, FD is associated with both cerebral macroangiopathy and microangiopathy, which leads to an increased incidence of stroke and first stroke at a younger age than the general population. Preliminary studies suggest that enzyme replacement therapy (e.g. agalsidase alfa or agalsidase beta) may reduce the risk of stroke.8
Fabry disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Enzyme replacement therapy has become the standard of care for patients with Fabry disease (63) It is ideally begun prior to the onset of symptoms, at least after 18 years of age in males. Products include agalsidase alfa (Replagal, Shire) and agalsidase (Sanofi Genzyme). The former is given (0.2 mg/kg) every other week, by intravenous injection. The latter is given (1 mg/kg) every other week intravenous.
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Fabry disease is a disorder linked to glycosphingolipid metabolism caused by α-galactosidase A (α-Gal) deficiency. The successful use of ERT for Fabry disease has been reported (Alfadhel and Sirrs, 2011). Recombinant agalsidase alfa and agalsidase beta have been compared for Fabry disease treatment (Arends et al., 2018). The authors found no difference between patients treated with either agalsidase, and a more pronounced reduction of storage materials was found with agalsidase beta.
Fabry disease – a multisystemic disease with gastrointestinal manifestations
Published in Gut Microbes, 2022
Treatment with either agalsidase-alfa (0.2 mg/kg b.w. e.o.w. intravenously; Replagal, Takeda) or agalsidase-beta (1.0 mg/kg b.w. e.o.w. intravenously; Fabrazyme, Sanofi Genzyme) was repeatedly reported to decrease frequencies of abdominal pain in affected adult and adolescent patients.20,21,23,32,59–63 Within the same studies, improvement of diarrhea,21,23,32,59,62 nausea and vomiting,21,60,62 and constipation21,62 were observed. In addition, the dose or compound might affect the outcome for GI symptoms. In this respect, patients who received a reduced dose of agalsidase-beta (0.3 to 0.5 mg/kg b.w. e.o.w. intravenously) or those who were switched from agalsidase-beta (1.0 mg/kg b.w.) to agalsidase-alfa (0.2 mg/kg b.w.) during the worldwide shortage of agalsidase-beta reported an increase of gastrointestinal pain.64 However, not all patients benefit from ERT, and GI symptoms are sometimes quite pronounced and relevant to daily life in ERT-treated patients, significantly reducing quality of life.
Long-term safety and efficacy of agalsidase beta in Japanese patients with Fabry disease: aggregate data from two post-authorization safety studies
Published in Expert Opinion on Drug Safety, 2021
Mina Tsurumi, Shinya Suzuki, Jiro Hokugo, Kazuo Ueda
The number of therapies available for patients with lysosomal storage diseases has expanded considerably in the past several years [15,16]. Enzyme replacement therapy (ERT) represents the mainstay of treatment for Fabry Disease, with two different human recombinant α-GAL ERTs developed for Fabry disease. Agalsidase beta (Fabrazyme®), a recombinant form of human α-GAL, has been approved for the treatment of Fabry disease in the European Union and United States since 2001 [17] and 2003 [18], respectively, and in Japan since 2004 [19]. The other ERT, agalsidase alfa, has been available in the European Union since 2001 [20] and Japan since 2006 [21]. Administration of these agents has been shown to result in marked increases in α-GAL A activity in human Fabry cells and Fabry mouse tissues; however, enzymatic activity in cultured fibroblasts, kidneys, heart, and spleen was higher for agalsidase beta compared with agalsidase alfa [22]. More recently, pharmacological chaperone therapies have become available, and substrate reduction therapies and gene therapy approaches are also in development, which are expected to improve outcomes for patients with Fabry disease [23].
The sweet spot for biologics: recent advances in characterization of biotherapeutic glycoproteins
Published in Expert Review of Proteomics, 2018
Róisín O’Flaherty, Irena Trbojević-Akmačić, Gordon Greville, Pauline M. Rudd, Gordan Lauc
Recombinant cytokines are used in a wide variety of infectious and autoimmune diseases, in immunocompromised patients with AIDS (acquired immune deficiency syndrome), and in neoplasia [6]. Recombinant human interferon-β 1a glycoproteins such as Avonex and Rebif are widely used as a first-line treatment for multiple sclerosis (MS) [7]. The native glycoprotein contains a single N-glycan site and the recombinant versions produced in Chinese Hamster Ovary (CHO) cells, mouse epithelial cells, and human lung adenocarcinoma cells all contain the most abundant native biantennary complex-type N-glycans present in the native glycoprotein [8]. Recently, glycoengineered variants have been produced using site-specific hyperglycosylation via site-directed mutagenesis to improve pharmacokinetic properties of the glycoprotein [7]. Therapeutic glycoproteins have also found applications in enzyme replacement therapies such as agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme) which have changed the treatment of Anderson-Fabry disease. The recombinant enzyme agalsidase alfa is produced in a cultured human cell line whereas the agalsidase beta is produced in CHO cells, both glycoproteins contain complex type N-glycans [9,10].