Clinical trial NCT05632484: Genotype Expression and Phenotype of Endothelial Cells, Carrying an ACVRL1, ENG or SMAD4 Mutation, in Response to BMP9 for the Identification of New Therapeutic Targets in Hereditary Haemorrhagic Telangiectasia
Official title: Genotype Expression and Phenotype of Endothelial Cells, Carrying an ACVRL1, ENG or SMAD4 Mutation, in Response to BMP9 for the Identification of New Therapeutic Targets in Hereditary Haemorrhagic Telangiectasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Haemorrhagic Telangiectasia
Keywords: hereditary haemorrhagic telangiectasia
endothelial cell
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 16
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome patients are carriers of a heterozygous mutation of the activin receptor-like kinase 1 (ACVRL1), Endoglin (ENG) or Mothers against decapentaplegic homolog 4 (SMAD4) gene. HHT involves the Bone Morphogenetic Protein 9 (BMP9)/Activin receptor-Like Kinase 1 (ALK1)-endoglin signalling pathway. BMP9 is a growth factor that binds to ALK1 receptor and to endoglin its co-receptors and physiologically activates Smad signaling pathway. Endothelial cells in HHT patients display half expression of functional ALK1 receptors or endoglin co-receptors or of the transcription factor SMAD4, which should lead to effects on the functions of these cells.

The identification of differences in gene expression between endothelial cells from HHT patients and healthy donors will allow the identification of new functions or new target pathways for therapy. Circulating endothelial cells are rare in the bloodstream in adults, but are present in greater quantities in cord blood.


Eligibility criteria: Inclusion Criteria:

* Newborn whose parents :

  * are adults
  * are affiliated to a social security or similar
  * are not subject to any legal protection measures
* Newborn child with one parent who has monitored for HHT confirmed by molecular biology (carrier of a mutation of the SMAD4, ENG or ACVRL1 gene).
* Consent signed by the two representatives of parental authority

Exclusion Criteria:

* One of the two parents opposes donating the umbilical cord blood and the umbilical cord for research
* One of the two parents opposes genetic testing
* Patient for whom it was not possible to obtain umbilical cord blood after delivery for technical or medical reasons.

Primary outcomes:
measure: Number of Endothelial Colony Forming Cells (ECFC) from cord blood
timeFrame: up to 3 weeks after cells isolation
measure: Number of Human Umbilical Vein Endothelial Cells(HUVEC) from cord
timeFrame: up to one week
Secondary outcomes:
measure: cell freezing and thawing
timeFrame: Through study completion, an average of 5 years.
measure: Gene expression quantification after RNA extraction from cells
timeFrame: Through study completion, an average of 5 years.
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Femme-mère-Enfant
city: Clermont-Ferrand
country: France
facility: Hôpital Estaing
city: Montpellier
country: France
facility: Hôpital St Eloi
Study officials:
References: