Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?

ABSTRACT: Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?

PROVIDER: PRJNA439302 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6871190.fastq.gz	Fastqsanger.gz
	SRR6871200.fastq.gz	Fastqsanger.gz
	SRR6871191.fastq.gz	Fastqsanger.gz
	SRR6871201.fastq.gz	Fastqsanger.gz
	SRR6871192.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 23

Similar Datasets

Does early treatment of PKU patients with sapropterin dihydrochloride affect brain development?

Project description:Background: Phenylketonuria (PKU) is an inborn error of metabolism caused by phenylalanine hydroxylase (PAH) deficiency. Patients with mild or moderate PKU can be successfully treated with sapropterin dihydrochloride (SD) which since recently is registered for usage from the age of 4 months. SD is a pharmaceutical version of tetrahydrobiopterin (BH4), a cofactor of PAH. Similar BH4 concentrations to those observed in plasma have been found in CSF of patients after a single oral administration thus proving that SD crosses the BBB. Hyperactivity has recently been reported as a post-marketing observation in some PKU patients treated with SD. Methods: 60 or 120 ng/ml sepiapterin, a stable precursor of BH4, were applied to study the effects of BH4 on developing brain cells in 3D organotypic rat brain cell cultures at two developmental stages. Immunohistochemistry, western blotting, metabolomics and RNA sequencing were performed. Findings: BH4 and BH2 measurements confirmed a successful conversion of sepiapterin to the active form BH4. In the earlier developmental stage, brain cell specific markers showed swollen astrocytes and diminished astrocytic fibres, delayed differentiation of oligodendrocytes and perturbation of axonal elongation. Immunofluorescence for activated caspase-3 revealed an increased apoptosis rate. We also found signs of perturbated GABAergic neurotransmission. RNAseq analyses revealed a number of significantly affected genes. GO enrichment allowed to identify key biological processes. Interestingly, none of these effects was observed in the later developmental stage. We show deleterious effects of SD on developing brain cells in a rat in vitro model. This observation raises the question whether the use of SD can be recommended in very young PKU patients as currently licensed.

2021-03-20 | GSE112108 | GEO

PKU Microbiome

Project description:The Adult Phenylketonuria (PKU) Gut Microbiome

| PRJEB42748 | ENA

Streptomyces sp. PKU-EA00015

Project description:Streptomyces sp. PKU-EA00015 Genome sequencing and assembly

| PRJNA641773 | ENA

Streptomyces sp. PKU-MA01144

Project description:Streptomyces sp. PKU-MA01144 Genome sequencing and assembly

| PRJNA627049 | ENA

Aspergillus sydowii strain:PKU 374

Project description:Aspergillus sydowii strain:PKU 374 Genome sequencing