Cellular and tissue distribution of intravenously administered agalsidase alfa

Murray, Gary J.; Anver, Miriam R.; Kennedy, Maureen A.; Quirk, Jane M.; Schiffmann, Raphael

doi:10.1016/j.ymgme.2006.11.008

Cited by 35 publications

(30 citation statements)

References 29 publications

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“…This is consistent with other studies of long-term ERT for FD, where persistent storage of GL3 has been demonstrated in vascular smooth muscle, stromal fibroblasts, pericytes and skeletal muscle fibres (Keslova-Veselikova et al 2008) and subtotal removal demonstrated in cultured skin fibroblasts (Askari et al 2007). GL3 clearance varies between different cell types (Murray et al 2007). Renal, myocardial and dermal endothelium clears after 5-6 months of ERT, and sustained clearance from vascular endothelium has been demonstrated after 30-36 months of ERT (Eng et al 2001;Wilcox et al 2004;Keslova-Veselikova et al 2008;Thurberg et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Carpal Tunnel Syndrome in Fabry Disease

et al. 2011

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Carpal tunnel syndrome (CTS) is a common peripheral mononeuropathy affecting up to 4% of the general population, typically women in late middle age. The incidence in patients with Fabry disease (FD) is unclear, but may affect 25% of patients with this X-linked lysosomal storage disease. We report three cases of CTS in young Caucasian male patients with classical FD, who developed CTS symptoms with supportive nerve conduction study (NCS) findings. Two patients had bilateral CTS and two had evidence of concurrent ulnar nerve neuropathy on NCS, suggesting a systemic process contributed to nerve compression. All were receiving enzyme replacement therapy (ERT) and had a moderate burden of FD complications. It is possible that an increase in connective tissue in the intracarpal canal in FD patients may be incited by injury to fibroblasts, via either accumulation of globotriaosylceramide (GL3) or local ischaemia through endothelial injury. The former hypothesis may be a more plausible explanation for the development of CTS, as histology of the flexor retinaculae from our patients has demonstrated fibroblasts with characteristic vacuolation and excessive myxomatous stroma, despite endothelial clearance of GL3 in these patients receiving ERT. CTS should not be overlooked in FD patients and young patients presenting with CTS should be evaluated for an underlying systemic or genetic disorder. Surgical carpal tunnel decompression was effective in our patients, already troubled by long-standing acroparesthesia, in providing sustained relief of symptoms.

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Section: Discussionmentioning

confidence: 99%

Carpal Tunnel Syndrome in Fabry Disease

et al. 2011

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“…Recently, detailed information was published on the relative tissue and cellular distribution of agalsidase alfa in a mouse knockout model of AFD (Murray et al 2007). Specific immunostaining for the recombinant enzyme was found in the liver, kidney, heart, testes, adrenal gland, spleen and bone marrow.…”

Section: Agalsidase Alfa and Special Considerationsmentioning

confidence: 99%

Agalsidase Alfa in the Treatment of Anderson-Fabry Disease

Pastores

2010

Fabry Disease

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Anderson-Fabry disease (AFD) is an X-linked storage disorder caused by a deficiency of the lysosomal hydrolase a-galactosidase A (AGAL) and the resultant accumulation of its glycosphingolipid substrate (Gb3) in several tissue types. Major morbidity and reduced life expectancy among affected individuals are a consequence of renal, cardiac and cerebrovascular involvement. Symptomatic males and females with AFD have been described, although the onset of clinical manifestations may be delayed and more variable among the latter patient group, partly attributed to lyonization. Agalsidase alfa (Replagal™) is a recombinant formulation of human AGAL which has been demonstrated to modify the course of AFD in treated patients. Factors that may influence clinical outcomes include disease stage at the point of treatment initiation and antibody formation. There is incomplete understanding of AFD pathophysiology. Early diagnosis and timely intervention may be essential. The use of adjunctive therapies, directed at risk reduction (eg, aspirin for stroke prophylaxis), require careful scrutiny, but such agents are likely to be vital components of a comprehensive approach to patient care. Long-term studies may clarify the optimal dose and frequency of enzyme administration. Meanwhile, budding strategies such as chaperone-mediated enzyme enhancement may offer the potential for an alternative or multimodality approach to the management of AFD.

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“…The reduction of Gb3 in the different groups of patients was found to be similar, and the authors concluded that, based on the effects on plasma Gb3 levels, increased dosages or frequency of dosing were not superior to the recommended dose of 0.2mg/kg every other week. Murray et al (2007) [48] studied the cellular and tissue distribution of agalsidase alfa in Fabry knock-out mice. Six mice received, by injection, a dose of 0.5mg of enzyme/kg body weight, and six other mice received vehicle only.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%