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New drugs for the treatment of Anderson–Fabry disease

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Abstract

Enzyme replacement therapy (ERT) of the Anderson–Fabry disease (AFD) has changed the outcome of patients. However, ERT has some limitations: a restricted volume of distribution, requirement for intravenous access, and stimulation of the production of anti-drug antibodies. Studies of new drugs aiming to improve the clinical effectiveness and convenience of therapy have been reported. Migalastat, a pharmacological chaperone, increases available enzymate activity in patients with mutations amenable to the therapy, is now available for clinical practice. It is orally administered, and while clinical trial results are promising, long term real world follow up is awaited. PEGylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations; investigation of whether a longer dosing interval is viable is under way. Moss-derived enzyme has a higher affinity for mannose receptors, and appears to have access to renal tissue. Substrate reduction therapy is based on reducing the catabolism processes of the glycosphingolipids, and is currently under investigation as monotherapy. Gene therapy has now been initiated in clinical trail of in vivo and ex vivo technologies with early results are emerging. ERT represents a certain milestone of therapy for AFD with Migalastat now a newly available option. Other agents in clinical trial prevent further potential opportunities to improve outcomes in AFD

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Authors and Affiliations

  1. Nephrology and Dialysis Unit, Belcolle Hospital, Via Sammartinese snc, 01100, Viterbo, Italy

    Sandro Feriozzi

  2. Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, UK

    Derralynn A. Hughes

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  1. Sandro Feriozzi
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  2. Derralynn A. Hughes
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Correspondence to Sandro Feriozzi.

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Conflict of interest

Sandro Feriozzi has received honoraria for advisory boards and travel expenses from Amicus, Sanofi Genzyme, and Takeda Shire*; received fees from Amicus, Otsuka, Sanofi Genzyme, and Takeda/Shire*. Deralynn Hughes has received travel and research grants and honoraria for speaking and advisory boards from Amicus, Genzyme, Protalix, and Shire.

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This manuscript is a review of previously published papers and there are no new, unpublished data. All data were reported in official journals in which it is declared that the studies have been approved by the appropriate institutional and/or national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This manuscript is a review of previously published papers and there are no new, unpublished data. In all papers it was reported that the informed consent of patients was obtained.

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Feriozzi, S., Hughes, D.A. New drugs for the treatment of Anderson–Fabry disease. J Nephrol 34, 221–230 (2021). https://doi.org/10.1007/s40620-020-00721-4

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