Characterization of a chemically modified plant cell culture expressed human Î±-Galactosidase-A enzyme for treatment of Fabry disease.

[fabry disease]

Fabry disease is an X-linked recessive disorder caused by the loss of function of the lysosomal enzyme Î±-Galactosidase-A . Although two enzyme replacement therapies (ERTs ) are commercially available , they may not effectively reverse some of the Fabry pathology . PRX -102 is a novel enzyme for the therapy of Fabry disease expressed in a BY 2 Tobacco cell culture . PRX -102 is chemically modified , resulting in a cross-linked homo-dimer . We have characterized the in -vitro and in -vivo properties of PRX -102 and compared the results with the two commercially produced Î±-Galactosidase-A enzymes . Results show that PRX -102 has prolonged in -vitro stability in plasma , after 1 h incubation it retains 30 % activity compared with complete inactivation of the commercial enzymes . Under lysosomal-like conditions PRX -102 maintains over 80 % activity following 10 days of incubation , while commercial enzymes become inactive after 2 days . Pharmacokinetic profile of PRX -102 measured in male Fabry mice shows a 10 fold increase in t 1 /2 in mice (581 min ) compared to approved drugs . The enzyme has significantly different kinetic parameters to the alternative ERTs available (p -value <0 .05 , one way ANOVA ), although these differences do not indicate any significant biochemical variations . PRX -102 is uptaken to primary human Fabry fibroblasts . The repeat administration of the enzyme to Fabry mice caused significant reduction (p -value <0 .05 ) of Gb 3 in various tissues (the measured residual content was 64 % in kidney , liver was cleaned , 23 % in heart , 5 .7 % in skin and 16 .2 % in spleen ). PRX -102 has a relatively simple glycosylation pattern , characteristic to plants , having mainly tri -mannose structures with the addition of either Î±(1 -3 )-linked fucose or Î² (1 -2 )-linked xylose , or both , in addition to various high mannose structures , while agalsidase beta has a mixture of sialylated glycans in addition to high mannose structures . This study concludes that PRX -102 is equivalent in functionality to the current ERTs available , with superior stability and prolonged circulatory half -life . Therefore we propose that PRX -102 is a promising alternative for treatment of Fabry disease .

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Diseases presenting "characteristic to plants" symptom

fabry disease

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