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GÈNES ET AUTISME - CELLULES SOUCHES PLURIPOTENTES INDUITES (IPSC)

EXPLORATIONS CELLULAIRES - CELLULES PLURIPOTENTES INDUITES DE SUJETS PRÉSENTANT UN TSA, DE LEURS APPARENTÉS, ET DE TÉMOINS

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and verbal and non-verbal communication (DSM-5, 2013), affecting approximately 2% of the general population. In 5 to 40% of cases, genetic factors are identified as the cause of these disorders, with prevalence depending on the technique used (exomes and/or SNP arrays) and the associated intellectual deficit. In the majority of cases, the etiology remains unknown. Studies of microdeletions/microduplications (copy number variants) or Whole Exome Sequencing and Whole Genome Sequencing (Single Nucleotide Variants) show the involvement of numerous genes in the predisposition to autism. ASD remains a genetically heterogeneous disorder, as more than 250 genes have been associated with ASD to date.

The main objective of the project is to continue identifying genetic factors, and also to understand the biological mechanisms involved in the emergence of autistic symptoms.

Identifying biological pathways is an essential step in developing new therapeutic strategies. In addition, one of the major challenges of this study is to better understand the phenotype/genotype relationships in ASD. This requires in-depth knowledge of the phenotypic characteristics of participants with ASD and their families, as well as neurotypical populations. This study combines the scientific expertise of researchers specializing in molecular biology, phenotypic exploration (clinical, cognitive, MRI, EEG, biochemistry, immunology), and the use of pre-therapeutic cellular models (iPSCs, neural precursors, organoids).

The objective of this work is the identification of numerous genes associated with ASD and involved in synaptic formation and regulation: NLGN3-4, SHANK1 and SHANK3, CNTN-6, and CNTNAP4. This work was combined with in-depth phenotypic explorations of ASD participants and their relatives. It has made it possible to clarify the neuroanatomical characteristics of participants with ASD and their genetic substrate, as well as the underlying cognitive processes.

All of this work opens up new prospects for identifying new therapeutic targets using preclinical cell models (IPSCs Induced pluripotent stem cells, neural progenitors, organoids) developed in particular by I-Stem and Human Technopole.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Description détaillée

  • Aim 1 : To clarify the biological mechanisms associated with genetic variations identified in participants with ASD by studying dedifferentiated cells transformed into induced neurons or organoids. This objective will be achieved using a population of individuals with ASD, a population of relatives and a population of controls.
  • Aim 2 : To study the cellular mechanisms affected by the presence of abnormalities identified in participants with ASD. The use of pluripotent cells differentiated into neurons or organoids is a major tool for understanding the pathophysiology of cell development and pathways in autism. These derived neurons are an indispensable proxy for the biological understanding of ASD.
  • Aim 3 : To identify new therapeutic approaches, by using pluripotent cells and organoids to perform high-throughput screening of pharmacological compounds.

Type d'étude

Interventionnel

Inscription (Estimé)

450

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

      • Paris, France, 75019
        • Hôpital Robert Debré
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

2 ans et plus (Enfant, Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

● For all participants :

  • 1) Be Included in the "Genes and Autism" protocol (C07-33 or C16-89).

  • 2) Affiliated to the social insurance, Universal Health Coverage or any equivalent system.

    →As a Reminder : C07-33 inclusion criteria

    ● Participants with ASD.

  • 1) Autistic patients must meet the diagnostic criteria of DSM-IV [American Psychiatric Association, 1994] and the criteria of ADI-R (Autism Diagnostic Interview-Revised, Lord et al., 1994) and ADOS for autism.

..Or.. Patients with Asperger's syndrome must meet the DSM-IV criteria as well as the ASDI criteria for Asperger's syndrome (Asperger Syndrome Diagnostic Interview, Gillberg et al., 2001) and the ADOS for autism spectrum disorders.

..Or.. Patients with ASD must meet diagnostic criteria of DSM-IV and ADOS criteria for autism spectrum disorders

  • 2) Be at least 2 years old, with no upper age limit

  • 3) Somatic state compatible with blood test

    ● Adult controls and adult relatives of controls

  • 1) Be between 18 and 65 years old

  • 2) Somatic and intellectual state compatible with blood test

    ● Controls with mental retardation

  • 1) Minimum age of 2 yearsIQ < 70Child controls

  • 2) Minimum age of 2 years

    →As a Reminder : inclusion criteria C16-89

    ● Probands with ASD

  • 1) Meet the diagnostic criteria for ASD of the of DSM-5 [American Psychiatric Association, 2012]. The diagnosis will be based on a consensus between the clinical expertise of expert clinicians, the scores of the Autism Diagnostic Interview-Revised (ADI-R) (Lord et al, 2003) and those of the Autism Diagnosis Observational Scale (ADOS-2) (Lord et al, 1994)

  • 2) Be at least 24 months old with no upper age limit

  • 3) Somatic state compatible with a blood test

  • 4) Affiliation to the Social Insurance

  • 5) Signature of informed consent by the applicant or by the holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

    ● Controls wihout ASD

  • 1) At least 24 months old

  • 2) Somatic and Intellectual state compatible with a blood test

  • 3) Affiliation in the Social Insurance

  • 4) Signature of informed consent by the subject or by holders of parental authority if the subject is a minor, or by the guardian if the subject is under guardianship

    ● Relatives of the probands with ASD or of controls without ASD

  • 1) At least 24 months old

  • 2) Somatic and intellectual state compatible with blood test

  • 3) Affiliation to the Social Insurance

  • 4) Signature of informed consent by the subject or by the holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Exclusion Criteria:

  • For all participants

    • 1) Refusal to have a blood test

    • 2) Medical illness (including psychiatric disorder) not yet fully stabilised and making participation in the study impossible

    • 3) Person subject to a mesure of lagal protection

    • 4) Known serology : VIH+ or VBH+ or VCH+

      • As a reminder : exclusion criteria C07-33
    • 1) For all participants : Severe Intelectual Deficiency (IQ,35 or developmental age <18 months)

    • 2) Controls : Neurological or psychiatric history other than mental retardation

      o Psychiatric history, except for mental retardation, assessed using the DIGS (Diagnostic Interview for Genetic Studies, Nurnberger et al., 1994) for adults or the Kiddie-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children, Orvaschel et al., 1982)

      o History of epileptic episodes

      o Immunosuppressive treatment or known immunoinflammatory disease

      →As a reminder : exclusion criteria C16-89

    • 1) Probands with Autism Spectrum Disorder

      o Severe intellectual disability (IQ<35 or developmental age <18 months)

    • 2) Controls (neurotypical development)

      o Identified intellectual disorder or cognitive developmental disorder

      • Personal psychiatric history of schizophrenia, bipolar disorder, substance use disorders (except tobacco), recurrent depression (>2 episodes, lifetime), severe unstabilized anxiety disorder
      • History of epilepsy episodes or severe neurological disease
    • 3) Relatives of the TSA applicants or controls

      • Medical condition (psychiatric or somatic) not compatible with inclusion

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Diagnostique
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Autre: Probands with Autism Spectrum Disorder, (N=200).

All subjects included in this study will be drawn from the population of subjects already included in the studies entitled 'Genes and Autism' promoted by Inserm (NCT02628808/C07-33 and NCT04727489/C16-89).

Patients are diagnosis ASD according to DSM-V criteria and carry genetic variations known to be associated with autism (whether rare or common).

Participation in this study requires a single visit per participant. This study only requires a blood sample (5 to 30 minutes) to be taken at the CIC at Robert-Debré Hospital, Paris 19th arrondissement.

This blood sample will enable the isolation of peripheral blood mononuclear cells (PBMCs). HIV, HCV and HBV serology will also be performed.

Autre: Controls without Autism Spectrum Disorder

At least, 24 months old (N=150) All subjects included in this study will be drawn from the population of subjects already included in the studies entitled 'Genes and Autism' promoted by Inserm (NCT02628808/C07-33 and NCT04727489/C16-89).

Participation in this study requires a single visit per participant. This study only requires a blood sample (5 to 30 minutes) to be taken at the CIC at Robert-Debré Hospital, Paris 19th arrondissement.

This blood sample will enable the isolation of peripheral blood mononuclear cells (PBMCs). HIV, HCV and HBV serology will also be performed.

Autre: Relatives of the probands with ASD

Adult relatives of controls with ASD (N=100) All subjects included in this study will be drawn from the population of subjects already included in the studies entitled 'Genes and Autism' promoted by Inserm (NCT02628808/C07-33 and NCT04727489/C16-89).

Participation in this study requires a single visit per participant. This study only requires a blood sample (5 to 30 minutes) to be taken at the CIC at Robert-Debré Hospital, Paris 19th arrondissement.

This blood sample will enable the isolation of peripheral blood mononuclear cells (PBMCs). HIV, HCV and HBV serology will also be performed.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Isolation of peripheral blood mononuclear cells (PBMCs)
Délai: Inclusion visit

Blood sample to be taken from individuals with ASD, a population of relatives, and a population of controls.

Inclusion visit

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Collaborateurs

Les enquêteurs

  • Directeur d'études: Thomas Pr Bourgeron, Professor, Institut Pasteur

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 décembre 2026

Achèvement primaire (Estimé)

1 février 2041

Achèvement de l'étude (Estimé)

1 août 2041

Dates d'inscription aux études

Première soumission

16 décembre 2025

Première soumission répondant aux critères de contrôle qualité

16 décembre 2025

Première publication (Réel)

30 décembre 2025

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

25 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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