Modelling urea cycle disorders using iPSCs.
Journal
NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846
Informations de publication
Date de publication:
26 Sep 2022
26 Sep 2022
Historique:
received:
03
02
2022
accepted:
10
08
2022
entrez:
26
9
2022
pubmed:
27
9
2022
medline:
27
9
2022
Statut:
epublish
Résumé
The urea cycle is a liver-based pathway enabling disposal of nitrogen waste. Urea cycle disorders (UCDs) are inherited metabolic diseases caused by deficiency of enzymes or transporters involved in the urea cycle and have a prevalence of 1:35,000 live births. Patients present recurrent acute hyperammonaemia, which causes high rate of death and neurological sequelae. Long-term therapy relies on a protein-restricted diet and ammonia scavenger drugs. Currently, liver transplantation is the only cure. Hence, high unmet needs require the identification of effective methods to model these diseases to generate innovative therapeutics. Advances in both induced pluripotent stem cells (iPSCs) and genome editing technologies have provided an invaluable opportunity to model patient-specific phenotypes in vitro by creating patients' avatar models, to investigate the pathophysiology, uncover novel therapeutic targets and provide a platform for drug discovery. This review summarises the progress made thus far in generating 2- and 3-dimensional iPSCs models for UCDs, the challenges encountered and how iPSCs offer future avenues for innovation in developing the next-generation of therapies for UCDs.
Identifiants
pubmed: 36163209
doi: 10.1038/s41536-022-00252-5
pii: 10.1038/s41536-022-00252-5
pmc: PMC9513077
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
56Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/T008024/1
Informations de copyright
© 2022. The Author(s).
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