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Pathology of Helicases and Premature Aging: Study by Derivation of hiPS (HeliPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03898817
Recruitment Status : Completed
First Posted : April 2, 2019
Last Update Posted : May 1, 2019
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief 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.

Condition or disease Intervention/treatment
Age Problem Other: taking of cutaneous cells

Detailed 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.

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Study Type : Observational
Actual Enrollment : 3 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Pathology of Helicases and Premature Aging: Study by Derivation of hiPS
Study Start Date : September 2015
Actual Primary Completion Date : September 2017
Actual Study Completion Date : March 2019

Group/Cohort Intervention/treatment
Taking of cutaneous cells by biopsy
Taking of cutaneous cells by biopsy and a sample of blood
Other: taking of cutaneous cells
Taking of cutaneous cells by biopsy Sample of blood

Primary Outcome Measures :
  1. Genomic instability : analysis [ Time Frame: 1 year ]
    Molecular analysis of hiPS cell derived from pathological tissue (karyotype, array-CGH)

  2. Genomic instability : size of telomers [ Time Frame: 1 year ]
    size of the telomers which will be quantified under microscope after fluorescent marking in situ of telomeric sequences (Q-FISH technique)

  3. Genomic instability : Duplication of centrosomes [ Time Frame: 1 year ]
    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.

Secondary Outcome Measures :
  1. cellular ageing : molecular analysis of hiPS cell derived from pathological tissue [ Time Frame: 2 years ]
    Analysis of senescence-associated heterochromatin foci, telomere length (Q-FISH)

  2. cellular ageing : IPS line with the criteria defined for morphological characterization [ Time Frame: 2 years ]
    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)

  3. cellular ageing : molecular characterization [ Time Frame: 2 years ]
    lengthening of telomeric sequence size (Q-FISH), re-expression of pluripotency genes (QRTPCR), transcriptional profile of iPS cell lines.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Population with pathology of helicases and premature aging

Inclusion Criteria:

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

Exclusion Criteria:

  • Minor and /or mentally incapable patient

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03898817

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University Hospital Montpellier
Montpellier, France, 34000
Sponsors and Collaborators
University Hospital, Montpellier
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Principal Investigator: Vincent GATINOIS, harmD University Hospital, Montpellier

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Responsible Party: University Hospital, Montpellier Identifier: NCT03898817     History of Changes
Other Study ID Numbers: 9360
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Montpellier:
induced pluripotent stem cells

Additional relevant MeSH terms:
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Aging, Premature
Signs and Symptoms