Role of ACTG2 Variants in Smooth Muscle Determination and Function in Pediatric Intestinal Pseudo-obstruction. (SMOOTH-PIPO)

Grenoble Alpes University Hospital Center (CHU)

Status: Not yet enrolling

Conditions: PIPO

Treatments: Procedure: Biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT06687564

2024-A01516-41 (Other Identifier)

38RC23.0368

Details and patient eligibility

About

The primary objective of this study is to describe the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene on iPS differentiation mechanisms up to organoids derived from PIPO patient samples versus those derived from control / WT patients (generation of IPS from cultured cell lines), at different stages of their experimental ex vivo development.

Full description

Recruited patients will be sampled during a consultation: a blood sample and a biopsy will be taken directly from the patient. Once these samples have been taken, they will be cultured to be reprogrammed into iPS cells, then grown and differentiated into intestinal organoids.

Various experiments will be carried out (as described in the outcomes) to identify at molecular, cellular and tissue level the mechanisms altered in patients with an R178, R257, R40 or A136 variant, assessing their consequence(s) on the development and functionality of the digestive mesenchyme.

Enrollment: 4 estimated patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

PIPO Population:

1. Minor or adult patient ≥ 4 years of age
2. Patient with PIPO before age 18
3. Male or female
4. Patient with PIPO meeting at least 2 of the ESPGHAN criteria (Thapar et al 2018) and carrying the R178, R257, R40 or A136 mutation of the ACTG2 gene.
5. Patient whose assent has been obtained and whose legal guardians have given their written informed consent
6. Patient affiliated to the French Social Security system or benefiting from an equivalent plan

WT population:

• iPS cell lines MS573 or WT8288 or 202CT or SD378M, from the Nantes University Hospital biological collection and generated from samples from control patients without POIC who have consented to donate their samples.

Exclusion criteria

PIPO population :

1. Patients with a history of radiotherapy treatment
2. Patient with lymphocyte lineage damage

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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4 participants in 2 patient groups

PIPO patients

Experimental group

Description:

PIPO patients with variants of interest

Treatment:

Procedure: Biopsy

WT

Other group

Description:

Control arm, same experiments as for patients. Samples from specific cell lines

Treatment:

Procedure: Biopsy