Pathology of Helicases and Premature Aging: Study by Derivation of hiPS

Age Problem Clinical Trial

— HeliPS  

Official title:

Pathology of Helicases and Premature Aging: Study by Derivation of hiPS

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03898817
• Other study ID #: 9360
• Status: Terminated
• Start date: September 9, 2015
• Est. completion date: September 9, 2017

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Topic of this work is the involvement of replicative helicases in human premature ageing syndrome. Replicative helicases are ubiquitous and essential during numerous reactions of the DNA metabolism.

The family of replicative helicases (RecQL) is involved in the replication/repair of the DNA and in the telomere maintenance. There are 5 enzymes in human and 3 of them are involved in clinically recognizable syndromes: WRN for the Werner syndrome, BLM for the Bloom syndrome and RECQL4 for the Rothmund Thomson syndrome. All are responsive of a high cancer risk due to genomic instability. Molecular and cellular mechanisms involved in these diseases of ageing are unknown. Moreover, for all of them, there is not therapeutic or preventive solution.

Description:

For understanding the involved mechanisms we would like to model the 3 diseases with hiPS (human induced Pluripotent Stem cells) from somatic cells of patients. The patient recruitment was organized by the Montpellier and Nîmes public hospitals.

The project is to generate a hiPS cell line for the 3 syndromes from fibroblasts and/or blood samples. Then, we could induce differentiation of hiPS to a target cell line of the diseases. Finally we could study the disease development following the genomic instability (karyotype, array-CGH) and the cellular ageing (senescence-associated heterochromatin foci, telomere length).

For each mutated enzyme, we will perform a transcriptional profiling (splice, mRNA quantification) and protein studies (western blot). All results will be compared to wild type cells.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 9, 2017
• Est. primary completion date: September 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patinet with one of the 3 helicase-associated precoce aging desease

Exclusion Criteria:

• Minor and /or mentally incapable patient

Related Conditions & MeSH terms

• Age Problem
• Aging, Premature

Intervention

Other:
• taking of cutaneous cells
Taking of cutaneous cells by biopsy Sample of blood

Locations

Country	Name	City	State
France	University Hospital Montpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genomic instability : analysis	Molecular analysis of hiPS cell derived from pathological tissue (karyotype, array-CGH)	1 year
Primary	Genomic instability : size of telomers	size of the telomers which will be quantified under microscope after fluorescent marking in situ of telomeric sequences (Q-FISH technique)	1 year
Primary	Genomic instability : Duplication of centrosomes	duplication of centrosomes which is often associated with chromosomal segregation errors and genomic instability. This analysis will be done by immunolabelling using antibodies specific to the 2 main components of centrosomes, pericentrin and -tubulin.	1 year
Secondary	cellular ageing : molecular analysis of hiPS cell derived from pathological tissue	Analysis of senescence-associated heterochromatin foci, telomere length (Q-FISH)	2 years
Secondary	cellular ageing : IPS line with the criteria defined for morphological characterization	expression of specific surface markers (specifics markers : TRA-1-60, SSEA-4), ability to re-differentiate in the 3 embryonic layers (specifics markers : SMA, MAP2, FOXA2)	2 years
Secondary	cellular ageing : molecular characterization	lengthening of telomeric sequence size (Q-FISH), re-expression of pluripotency genes (QRTPCR), transcriptional profile of iPS cell lines.	2 years