New therapeutics for primary hyperoxaluria type 1.
Journal
Current opinion in nephrology and hypertension
ISSN: 1473-6543
Titre abrégé: Curr Opin Nephrol Hypertens
Pays: England
ID NLM: 9303753
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
pubmed:
11
3
2022
medline:
24
6
2022
entrez:
10
3
2022
Statut:
ppublish
Résumé
Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that causes hepatic overproduction of oxalate and, often, nephrocalcinosis, nephrolithiasis, chronic kidney disease, and kidney failure. The purpose of the review is to provide an update on current emerging therapies for the treatment of PH1. Use of ribonucleic acid interference (RNAi) therapeutics that target the liver to block production of key enzymes along pathways that generate oxalate is a promising approach. Available evidence supports the efficacy of both Lumasiran (targeting glycolate oxidase) and Nedosiran (targeting hepatic lactate dehydrogenase (LDHa)) to reduce urinary oxalate excretion in PH1. The efficacy of alternative approaches including stiripentol (an anticonvulsant drug that also targets LDHa), lanthanum (a potential gastrointestinal oxalate binder), and Oxalobacter formigenes (a bacterium that can degrade oxalate within the gastrointestinal tract and may also increase its secretion from blood) are all also under study. Genetic editing tools including clustered regularly interspaced short palindromic repeats/Cas9 are also in preclinical study as a potential PH1 therapeutic. Novel treatments can reduce the plasma oxalate concentration and urinary oxalate excretion in PH1 patients. Thus, it is possible these approaches will reduce the need for combined kidney and liver transplantation to significantly decrease the morbidity and mortality of affected patients.
Identifiants
pubmed: 35266883
doi: 10.1097/MNH.0000000000000790
pii: 00041552-202207000-00009
pmc: PMC9232952
mid: NIHMS1784049
doi:
Substances chimiques
Oxalates
0
RNA, Small Interfering
0
L-Lactate Dehydrogenase
EC 1.1.1.27
lumasiran
RZT8C352O1
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
344-350Subventions
Organisme : NCATS NIH HHS
ID : R21 TR003174
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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