Pathology of Helicases and Premature Aging: Study by Derivation of hiPS (HeliPS)
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Montpellier, Francia, 34000
- University Hospital Montpellier
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Patinet with one of the 3 helicase-associated precoce aging desease
Exclusion Criteria:
- Minor and /or mentally incapable patient
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: Otro
- Perspectivas temporales: Futuro
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
Taking of cutaneous cells by biopsy
Taking of cutaneous cells by biopsy and a sample of blood
|
Taking of cutaneous cells by biopsy Sample of blood
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Genomic instability : analysis
Periodo de tiempo: 1 year
|
Molecular analysis of hiPS cell derived from pathological tissue (karyotype, array-CGH)
|
1 year
|
|
Genomic instability : size of telomers
Periodo de tiempo: 1 year
|
size of the telomers which will be quantified under microscope after fluorescent marking in situ of telomeric sequences (Q-FISH technique)
|
1 year
|
|
Genomic instability : Duplication of centrosomes
Periodo de tiempo: 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.
|
1 year
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
cellular ageing : molecular analysis of hiPS cell derived from pathological tissue
Periodo de tiempo: 2 years
|
Analysis of senescence-associated heterochromatin foci, telomere length (Q-FISH)
|
2 years
|
|
cellular ageing : IPS line with the criteria defined for morphological characterization
Periodo de tiempo: 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)
|
2 years
|
|
cellular ageing : molecular characterization
Periodo de tiempo: 2 years
|
lengthening of telomeric sequence size (Q-FISH), re-expression of pluripotency genes (QRTPCR), transcriptional profile of iPS cell lines.
|
2 years
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Vincent GATINOIS, harmD, University Hospital, Montpellier
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 9360
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .