Genotype-phenotype Characterization Study on Genetic Diseases With Immune and Neurological Dysfunctions (IFN)

Over the past twenty years, Prof. Yanick Crow and his team have developed internationally recognized expertise in genetic pathologies affecting the immune and neurological systems. The pathologies studied have a particularly severe impact on patients' quality of life, with a high mortality rate and a significant risk of occurrence in affected families. These pathologies are rare, and very often under-diagnosed. To date, there is virtually no effective curative treatment.

Prof. Crow's team operates at the frontier between clinical and research work, and from experience, the team knows that patients and families affected by these serious pathologies are often highly motivated to help research into the pathology that affects them.

Initially, Prof. Crow's research focused primarily on the study of the genetic disease Aicardi-Goutières Syndrome (AGS). However, there is an undeniable clinical and pathological overlap between AGS and other forms of disease such as autoimmune systemic lupus erythematosus and many other genetic pathologies - e.g. familial lupus engelure, spondyloenchondromatosis and COPA syndrome. This is why research is being extended to all genetic diseases with immune and neurological dysfunctions.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; Genetic Diseases; Neurological Disease; Immune Dysfunction
• Intervention / Treatment: Other: Biological Samples

Detailed Description

The research methodology is classic with regard to many genetic clinical studies, and aims to:

• clinically define the phenotypes of these diseases (in this case, genetic diseases with immune and neurological dysfunctions)
• identify the gene(s) responsible for each disease
• Understand how changes in these genes and protein functions cause these diseases.

It is possible that this research will ultimately lead to the creation of diagnostic tests (e.g. molecular diagnostic screening tests) and treatments that would be clinically very useful for the patients participating in the project. These discoveries could also improve our knowledge of other more common pathologies, particularly those associated with autoimmunity (e.g. when the body increases an immune response against its own tissues).

As a complement to this global research project, Prof. Crow's team intends to study cell populations from patients with no inflammatory pathology, in order to analyze their basal levels of immune and inflammatory mediator production, as well as to assess their capacity (kinetics and amplitude) to respond to stimuli.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Yanick Crow, MD PhD; Email: yasmine.ainouz@institutimagine.org
• Study Contact Backup: Name: Marie-Louise Frémond, MD PhD

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75015
      • Recruiting
      • Necker Enfants malades hospital
      • Contact: Yannick Crow, MD PhD; Email: yanickcrow@mac.com
      • Contact: Marie-Louise Frémond, MD, PhD; Email: marie-louise.fremond@institutimagine.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be included by any hospital department involved in the management of these pathologies in France.

Description

Inclusion criteria

• Patients :

  • Have / present a family history of genetic disease with immune and neurological dysfunction.
  • Have signed an informed consent form.

• Unaffected related subjects :

  • Be related to a patient included in this research.
  • Have signed an informed consent form.

• Control patients

  • Be free of any genetic disease with immune and neurological dysfunction.
  • Have undergone surgery as part of their management
  • Have signed an informed consent form.

Non-inclusion criteria

✓ Be deprived of liberty

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls	Other: Biological Samples; For patients, different types of banked frozen or fresh biological samples will be used in this research: Blood; Skin biopsy or other tissues (liver, muscle, brain, lung...); Urine; Saliva; Cerebrospinal fluid; Occasionally: operative "leftovers" (e.g. muscle, brain, lung tissue) In control patients, we would like to collect operative remnants of cell types involved in the inflammatory and/or neurological diseases studied in the laboratory, if these patients require surgery as part of their management, and if any biological material remains after surgery. Under the same conditions, a sample of cerebrospinal fluid could be recovered. For unaffected relatives, a single blood sample of maximum 10 ml is taken at inclusion, and samples already taken during routine care are used.
Patients	Other: Biological Samples; For patients, different types of banked frozen or fresh biological samples will be used in this research: Blood; Skin biopsy or other tissues (liver, muscle, brain, lung...); Urine; Saliva; Cerebrospinal fluid; Occasionally: operative "leftovers" (e.g. muscle, brain, lung tissue) In control patients, we would like to collect operative remnants of cell types involved in the inflammatory and/or neurological diseases studied in the laboratory, if these patients require surgery as part of their management, and if any biological material remains after surgery. Under the same conditions, a sample of cerebrospinal fluid could be recovered. For unaffected relatives, a single blood sample of maximum 10 ml is taken at inclusion, and samples already taken during routine care are used.
Unaffected related subjects	Other: Biological Samples; For patients, different types of banked frozen or fresh biological samples will be used in this research: Blood; Skin biopsy or other tissues (liver, muscle, brain, lung...); Urine; Saliva; Cerebrospinal fluid; Occasionally: operative "leftovers" (e.g. muscle, brain, lung tissue) In control patients, we would like to collect operative remnants of cell types involved in the inflammatory and/or neurological diseases studied in the laboratory, if these patients require surgery as part of their management, and if any biological material remains after surgery. Under the same conditions, a sample of cerebrospinal fluid could be recovered. For unaffected relatives, a single blood sample of maximum 10 ml is taken at inclusion, and samples already taken during routine care are used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical features of human genetic diseases that affect the immune and neurological systems.	Clinical features of human genetic diseases that affect the immune and neurological systems.	through study completion, an average of 1 year
Natural history of human genetic diseases that affect the immune and neurological systems.	Natural history of human genetic diseases that affect the immune and neurological systems.	through study completion, an average of 1 year
Molecular and cellular basis of human genetic diseases that affect the immune and neurological systems.	Molecular and cellular basis of human genetic diseases that affect the immune and neurological systems.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Imagine Institute
• Investigators: Principal Investigator: Yanick Crow, MD PhD, Imagine Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Genetic Diseases, Inborn
• Other Study ID Numbers: IMNIS2014-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No