Immune tolerant Fabry mouse by liver restricted expression become the inevitable material to study efficacy in enzyme replacement therapy with a modified .-N-acetylgalactosaminidase

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Previous studies have shown that modified human .-N-acetylgalactosaminidase (NAGA) with human .-galactosidase A (GLA)-like substrate specificity prevents globotriaosylceramide (Gb3) storage in Fabry model mouse. Furthermore, this modified NAGA is hardly expected to cause an allegic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for enzyme replacement therapy (ERT) for Fabry disease. Surprisingly, a modified NAGA intravenously injected into Fabry model mice was associated with a high rate of fatal anaphylaxis. Here, we reported that suppression of allegic reaction can be achieved in vivo by taking advantage of ability of the liver to promote immune tolerance. Expression of NAGA in the liver was accomplished stably in liver-specific NAGA transgenic (NAGA-Tg) Fabry model mice. Therefore, immune tolerant NAGA-Tg Fabry model mice could become the inevitable materials to study evaded immunity and enhanced efficacy in ERT with a modified NAGA.