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01-02-2019 | Invited Review

Molecular basis of primary hyperoxaluria: clues to innovative treatments

Authors: Mirco Dindo, Carolina Conter, Elisa Oppici, Veronica Ceccarelli, Lorella Marinucci, Barbara Cellini

Published in: Urolithiasis | Issue 1/2019

Abstract

Primary hyperoxalurias (PHs) are rare inherited disorders of liver glyoxylate metabolism, characterized by the abnormal production of endogenous oxalate, a metabolic end-product that is eliminated by urine. The main symptoms are related to the precipitation of calcium oxalate crystals in the urinary tract with progressive renal damage and, in the most severe form named Primary Hyperoxaluria Type I (PH1), to systemic oxalosis. The therapies currently available for PH are either poorly effective, because they address the symptoms and not the causes of the disease, or highly invasive. In the last years, advances in our understanding of the molecular bases of PH have paved the way for the development of new therapeutic strategies. They include (i) substrate-reduction therapies based on small-molecule inhibitors or the RNA interference technology, (ii) gene therapy, (iii) enzyme administration approaches, (iv) colonization with oxalate-degrading intestinal microorganisms, and, in PH1, (v) design of pharmacological chaperones. This paper reviews the basic principles of these new therapeutic strategies and what is currently known about their application to PH.

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Title: Molecular basis of primary hyperoxaluria: clues to innovative treatments
Authors: Mirco Dindo
Carolina Conter
Elisa Oppici
Veronica Ceccarelli
Lorella Marinucci
Barbara Cellini
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Urolithiasis / Issue 1/2019
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-018-1089-z

At a glance: The STEP trials

Springer Medicine

Molecular basis of primary hyperoxaluria: clues to innovative treatments

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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