Pseudoxanthoma Elasticum
Conditions
Keywords
PXE, renal cells, urine, calcification, omics, drug screening
Brief summary
Our objective is to obtain human induced pluripotent stem cells from urine samples of PXE patients for further proteomic and metabolomic studies and treatment screening.
Detailed description
Pseudoxanthoma elasticum (PXE) is a genetic multysystem disorder with cutaneous, ophtalmological and cardiovascular involvement. PXE is associated with mutations of ABCC6 gene coding for the membrane transporter ABCC6 protein. This transporter is normally expressed in hepatocytes and epithelial cells of renal proximal convoluted tubules. Thus, PXE could be regarded as a metabolic disease of hepatic and renal origin, with clinical and biological involvement/consequences for remote organs. The substance transported by ABCC6 protein being still unknown, ethiological PXE treatment does not exist yet. However, ABCC6 deficiency is associated with low level of blood PPi (pyrophosphate), which is natural inhibitor of calcium-phosphate deposition. The aim of the project is to obtain the renal cells derived from PXE patients for their further usage in proteomic and metabolomic studies, as well as for screening of treatment modalities aimed to correct ABCC6 functional deficiency.
Interventions
OTHERurine collection
3 urine collections during 24 hours
Sponsors
Université de Nantes
Hungarian Academy of Sciences
University Hospital, Angers
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with PXE diagnosed on clinical and histological criteria, according to current guidelines * Patient aged over 18 * Patient informed, having understood the purpose and means of the study and signed the consent of participation * Patient affiliated to the French social welfare system
Exclusion criteria
* Pregnant or nursing PXE woman * Patient under guardianship, deprived of liberty by court or administrative decision, hospitalized without consent or admitted to a health or social institution for purposes other than research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine collection | 24 hours | Three urine samples in each PXE in-patient consequences of the functional deficiency of the ABCC6 transporter involved in the pathophysiology of PXE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Isolation and culture of renal cells | 8 weeks | According to the routine procedure of our lab |
| Impact of ABCC6 mutations on renal cell functions | 3 months | Proteomic and metabolomic and RNAseq approaches |
| High throughput screening of drugs to restore ABCC6 function in PXE patients renal cells | 3 months | Evaluation of PPi release and other relevant readouts |
Outcome results
None listed