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GENES AND AUTISM - IPSC (IPSC)

세포 연구 - 자폐 스펙트럼 장애(ASD)를 가진 대상자, 그 친척 및 대조군으로부터 유도된 만능 세포

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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

  • 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.

연구 유형

중재적

등록 (추정된)

450

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

      • Paris, 프랑스, 75019
        • Hôpital Robert Debré
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

2년 이상 (어린이, 성인, 고령자)

건강한 자원 봉사자를 받아들입니다

예

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 특수 증상
  • 할당: 무작위화되지 않음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
다른: 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.

다른: 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.

다른: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Isolation of peripheral blood mononuclear cells (PBMCs)
기간: Inclusion visit

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

Inclusion visit

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

협력자

수사관

  • 연구 책임자: Thomas Pr Bourgeron, Professor, Institut Pasteur

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 12월 1일

기본 완료 (추정된)

2041년 2월 1일

연구 완료 (추정된)

2041년 8월 1일

연구 등록 날짜

최초 제출

2025년 12월 16일

QC 기준을 충족하는 최초 제출

2025년 12월 16일

처음 게시됨 (실제)

2025년 12월 30일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 25일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 24일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

  • C22-14

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .