" Development of Primary Cultures of Diaphragmatic Myoblasts for Basic Research Purposes " (MYODiaph)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Endometriosis

Treatments: Other: During the surgery planned as part of the routine care of the patient, a part of the tissue sample will be saved in order to carry out the analysis planned for the research.

Study type: Observational

Funder types: Other

Identifiers

NCT07380308

APHP250977

2024-A02556-41 (Other Identifier)

Details and patient eligibility

About

Neuromuscular diseases (NMDs) affecting motor neurons (MN) induce progressive muscle denervation, and become fatal when respiratory muscles e.g. the diaphragm are affected and can no longer contract. In some cases, such as Charcot's disease (Amyotrophic lateral sclerosis-ALS), there is no cure and patients die due to respiratory failure few years after diagnosis. Investigations on NMD-induced alterations of respiratory muscles in humans are limited notably by the absence of available in vitro model based on cell cultures of diaphragm-derived myoblasts. Yet, this cell tool is likely to help in developing original therapies to limit diaphragm muscle atrophy and dysfunction in NMD. To date, only cell cultures of human myoblasts obtained from limb muscles are available, making difficult to transpose results to the diaphragm.

Thus, in the present project, we propose to :

1. originally develop primary cultures of myoblasts from human diaphragm, obtained from surgical resection of diaphragmatic endometriosis,
2. characterize them in terms of differentiation status (Histology, IF), metabolism (Metabolomics by NMR, cell respiration), and gene expression (RNASeq), in comparison to primary myoblasts cultures derived from the deltoid already available in the team.

This project will provide an original new tool and important data on the specificity of diaphragm-derived myoblasts, compared to limb muscle-derived myoblasts with the long-term perspective of opening new therapeutical pathways for patients with severe NMDs.

Full description

Neuromuscular diseases (NMDs) affecting motor neurons (MN) induce progressive muscle denervation, and become fatal when respiratory muscles e.g. the diaphragm are affected and can no longer contract. In some cases, such as Charcot's disease (Amyotrophic lateral sclerosis-ALS), there is no cure and patients die due to respiratory failure few years after diagnosis. Investigations on NMD-induced alterations of respiratory muscles in humans are limited notably by the absence of available in vitro model based on cell cultures of diaphragm-derived myoblasts. Yet, this cell tool is likely to help in developing original therapies to limit diaphragm muscle atrophy and dysfunction in NMD. To date, only cell cultures of human myoblasts obtained from limb muscles are available, making difficult to transpose results to the diaphragm.

Thus, in the present project, we propose to :

1. originally develop primary cultures of myoblasts from human diaphragm, obtained from surgical resection of diaphragmatic endometriosis,
2. characterize them in terms of differentiation status (Histology, IF), metabolism (Metabolomics by NMR, cell respiration), and gene expression (RNASeq), in comparison to primary myoblasts cultures derived from the deltoid already available in the team.

This project will provide an original new tool and important data on the specificity of diaphragm-derived myoblasts, compared to limb muscle-derived myoblasts with the long-term perspective of opening new therapeutical pathways for patients with severe NMDs.

Enrollment: 10 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Age ≥ 18 years
• diaphragmatic endometriosis requiring surgical resection of the nodules in the diaphragm.
• Collection of non-opposition

Exclusion Criteria

• Inability to speak and/or read French
• Patients under tutor or curatorship
• Protected adults

Trial design

10 participants in 1 patient group

Patients

Description:

Patients with endometriosis requiring surgical nodules resection in the diaphragm.

Treatment:

Other: During the surgery planned as part of the routine care of the patient, a part of the tissue sample will be saved in order to carry out the analysis planned for the research.