Modelling urea cycle disorders using iPSCs
Abstract 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 acut...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00252-5 |
| _version_ | 1828167499191943168 |
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| author | Claire Duff Julien Baruteau |
| author_facet | Claire Duff Julien Baruteau |
| author_sort | Claire Duff |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T02:18:35Z |
| format | Article |
| id | doaj.art-102d60ad66214f22b286647e9bdcb583 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-04-12T02:18:35Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-102d60ad66214f22b286647e9bdcb5832022-12-22T03:52:12ZengNature Portfolionpj Regenerative Medicine2057-39952022-09-01711910.1038/s41536-022-00252-5Modelling urea cycle disorders using iPSCsClaire Duff0Julien Baruteau1Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College LondonAbstract 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.https://doi.org/10.1038/s41536-022-00252-5 |
| spellingShingle | Claire Duff Julien Baruteau Modelling urea cycle disorders using iPSCs npj Regenerative Medicine |
| title | Modelling urea cycle disorders using iPSCs |
| title_full | Modelling urea cycle disorders using iPSCs |
| title_fullStr | Modelling urea cycle disorders using iPSCs |
| title_full_unstemmed | Modelling urea cycle disorders using iPSCs |
| title_short | Modelling urea cycle disorders using iPSCs |
| title_sort | modelling urea cycle disorders using ipscs |
| url | https://doi.org/10.1038/s41536-022-00252-5 |
| work_keys_str_mv | AT claireduff modellingureacycledisordersusingipscs AT julienbaruteau modellingureacycledisordersusingipscs |