Biological Collection of Kidney Cells

Pseudoxanthoma Elasticum Clinical Trial

— CRHiPS  

Official title:

Biological Collection of Renal Cells for the Functional Study of the ABCC6 Transporter on iPS-derived Hepatocytes and Renal Cells

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03364504
• Other study ID #: 49RC17_0063
• Status: Not yet recruiting
• Phase: N/A
• First received: July 11, 2017
• Last updated: December 5, 2017
• Start date: January 2018
• Est. completion date: December 2018

Study information

• Verified date: June 2017
• Source: University Hospital, Angers
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pseudoxanthoma Elasticum

Intervention

Other:
• urine collection
3 urine collections during 24 hours

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Angers	Hungarian Academy of Sciences, Université de Nantes

References & Publications (4)

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. Epub 2005 May 13. Review. — View Citation

Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi 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 sys — View Citation

Jansen RS, Küçükosmanoglu 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 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine collection	Three urine samples in each PXE in-patient consequences of the functional deficiency of the ABCC6 transporter involved in the pathophysiology of PXE	24 hours
Secondary	Isolation and culture of renal cells	According to the routine procedure of our lab	8 weeks
Secondary	Impact of ABCC6 mutations on renal cell functions	Proteomic and metabolomic and RNAseq approaches	3 months
Secondary	High throughput screening of drugs to restore ABCC6 function in PXE patients renal cells	Evaluation of PPi release and other relevant readouts	3 months