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 (CAERO)

Civil Hospices of Lyon

Status: Completed

Conditions: Hereditary Haemorrhagic Telangiectasia

Treatments: Biological: Cord blood sampling; Biological: Cord sampling

Study type: Interventional

Funder types: Other

Identifiers

NCT05632484

2021-A01792-39 (Other Identifier)

69HCL20_0250

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Newborns with a parent with HHT disease

Experimental group

Description:

16 newborns with one parent suffering HHT disease and carrying a mutation in the ACVRL1, ENG or SMAD4 gene will be included in this study.

Treatment:

Biological: Cord sampling

Biological: Cord blood sampling

Biological: Cord blood sampling