Clinical trial NCT03364504: Biological Collection of Kidney Cells
Official title: Biological Collection of Renal Cells for the Functional Study of the ABCC6 Transporter on iPS-derived Hepatocytes and Renal Cells
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pseudoxanthoma Elasticum
Keywords: PXE
renal cells
urine
calcification
omics
drug screening
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Université de Nantes
name: Hungarian Academy of Sciences
First posted: 2017-12-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Urine collection
timeFrame: 24 hours
Secondary outcomes:
measure: Isolation and culture of renal cells
timeFrame: 8 weeks
measure: Impact of ABCC6 mutations on renal cell functions
timeFrame: 3 months
measure: High throughput screening of drugs to restore ABCC6 function in PXE patients renal cells
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
References:
citation: Si-Tayeb K, Idriss S, Champon B, Caillaud A, Pichelin M, Arnaud L, Lemarchand P, Le May C, Zibara K, Cariou B. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia. Dis Model Mech. 2016 Jan;9(1):81-90. doi: 10.1242/dmm.022277. Epub 2015 Nov 19.
citation: Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet. 2005 Dec;42(12):881-92. doi: 10.1136/jmg.2004.030171. Epub 2005 May 13.
citation: Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Varadi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26.
citation: Jansen RS, Kucukosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25.