Patients With RETT Syndrome (RETT)

Study of Biological Parameters in 100 Girls With RETT Syndrome

It was proposed to the French Association of Rett Syndrome (AFSR) to perform an extensive biological assessment in a series of 100 girls with Rett's syndrome and carriers of a mutation in the MECP2 gene in order to confirm or confirm to reverse the abnormalities identified previously and possibly, to highlight new biomarkers of the pathology. The analysis will focus on classical hematological criteria, iron markers, endocrine assays, lipid quantification and markers of inflammation. At the end of the project, each family will receive the complete biological assessment carried out on their daughter which will represent a direct benefit of the implication in this clinical research project.

Study Overview

• Status: Unknown
• Conditions: Rett Syndrome
• Intervention / Treatment: Other: An extensive biological assessment

Detailed Description

The MECP2 (Methyl-CpG binding protein) gene, located on the X X28 chromosome, encodes a heterochromatin nuclear protein. Mecp2 is preferentially found in neurons at a postmitotic stage where it promotes brain development. Its ability to fix methylated DNA and contribute to the formation of a transcriptional repression complex attributes this protein to a crucial role in the control of gene expression. However, until today, its exact role is not known. In humans, mutations in the MECP2 gene are at the origin of neurological diseases, the main one being Rett's syndrome (RTT-MIM # 312750) where a mutation of MECP2 is found in 95% of cases. This dominant pathology linked to the X chromosome has a prevalence of 1/10000 to 1/15000 births and affects mostly girls. The course of the pathology is characterized by a cessation of development between 6 and 18 months after birth. Patients present a set of characteristic signs including regression of acquired abilities, manual stereotyping, loss of language, behavioral disorders and severe intellectual disability. In their attempt to better understand the pathology, many laboratories are currently trying to identify abnormal biological parameters in patients that are easy to identify in a non-invasive or minimally invasive way in order to indirectly evaluate the progression of the pathology and to identify biochemical disorders amenable to direct pharmacological intervention.

In autumn 2015, several factors were identified as deregulated in model mice or RTT patients (Rett syndrome). They could be related to the severity of the disease and indicators of its progression. Among these we can mention:

• major structural damage to red blood cells;
• Inflammation demonstrated and challenged ;
• high oxidative stress markers; lipid deregulation and in particular cholesterol abnormalities;
• a deficiency of the signaling pathway of insulin and IGF-1.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: DRS AP-HM; Email: drci@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille
    • Contact: Mathieu Milh; Phone Number: 0491386807; Email: mathieu.milh@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• People with Rett syndrome related to MECP2 gene mutation
• Aged under 18 years old.
• Regularly followed as part of their illness by Prof. Bahi-Buisson in Necker or Pr Milh in Marseille.
• Whose state of health justifies a blood test (dosage of one or more anti-epileptics, recommended annual phosphocalcic balance, pre-therapeutic assessment before introduction of a new molecule ...)
• Whose at least one parent (or legal representative) has signed the consent
• Patient fasting for 6 hours at the time of sampling.

Exclusion Criteria:

• Contraindication to a balance sheet
• Absence of consent of the legal representatives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Girls with RETT syndrome; 100 girls over 18 years old with RETT syndrome	Other: An extensive biological assessment; To study the morphology of red blood cells, the markers of oxidative stress and the signaling pathway of IFGF1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of red blood cell morphology	Identification of abnormal red blood cells	1 day
Comparison of oxydative stress markers	Identification of abnormally high cytokine levels	1 day
Comparison of cholesterol levels	Identification of hight cholesterol levels	1 day

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: 2018-30; 2018-A01066-49 (Registry Identifier: ANSM)

Drug and device information, study documents

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