Engineering Organoids for in vitro Modeling of Phenylketonuria

Alice C. Borges, Kerensa Broersen, Paula Leandro, Tiago G. Fernandes*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

2 Citations (Scopus)


Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.

Original languageEnglish
Article number787242
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 10 Jan 2022


  • disease modeling
  • human induced pluripotent stem cells
  • neurodegeneration
  • neurodevelopment
  • organoids
  • phenylketonuria


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