Agalsidase alfa for the treatment of fabry disease: a closer look

Lipinski, Shawn E.; Komlódi-Pásztor, Edina; Göker-Alpan, Özlem

doi:10.4155/cli.14.35

Cited by 1 publication

(1 citation statement)

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“… 12 , 13 Two ERT-based treatments are human recombinant forms of α-galactosidase A (agalsidase), known as agalsidase-α (Replagal, Shire, Lexington, MA) and agalsidase-β (Fabrazyme, Sanofi-Genzyme, Cambridge, MA), which are each administered intravenously once every other week and provide beneficial effects toward slowing the progression of the disease. 14 , 15 , 16 , 17 While therapeutic value has been demonstrated through this approach, there are challenges associated with ERT and unmet medical needs still remain. Such challenges include variability of response, immunogenicity of the recombinant protein resulting in antibody generation (including neutralizing), infusion reactions, and difficulties inherent with cell-based manufacturing such as robust reproducibility of proper glycosylation patterns.…”

Section: Introductionmentioning

confidence: 99%

Improved Efficacy in a Fabry Disease Model Using a Systemic mRNA Liver Depot System as Compared to Enzyme Replacement Therapy

et al. 2019

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Fabry disease is a lysosomal storage disorder caused by the deficiency of a-galactosidase A. Enzyme deficiency results in a progressive decline in renal and cardiac function, leading to cardiomyopathy and end-stage renal disease. Current treatments available, including enzyme replacement therapies, have provided significant benefit to patients; however, unmet medical needs remain. mRNA therapy, with drug-like properties, has the unique ability to produce therapeutic proteins endogenously. Here we describe the sustained delivery of therapeutic human a-galactosidase protein in vivo via nanoparticle-formulated mRNA in mouse and non-human primate, with a demonstration of efficacy through clinically relevant biomarker reduction in a mouse Fabry disease model. Multi-component nanoparticles formulated with lipids and lipid-like materials were developed for the delivery of mRNA encoding human a-galactosidase protein. Upon delivery of human GLA mRNA to mice, serum GLA protein levels reached as high as $1,330-fold over normal physiological values.

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