Phosphoproteomic Profile of Children With Down Syndrome

Perha Pharmaceuticals60 enrolled

Overview

One of the major causes of cognitive disorders limiting the learning abilities of children with Down's syndrome is excess activity of the DYRK1A protein kinase, whose gene is located on chromosome 21. Consequently, variations in the level of phosphorylation, and hence activity, of DYRK1A target proteins involved in synaptic transmission, could identify mechanisms underlying these cognitive disorders. Several studies have shown that plasma proteins can reflect a pathophysiological brain state. The investigators plan to carry out a phosphoproteomic study to determine the phosphorylation profile of plasma proteins in children with Down's syndrome, and identify potential DYRK1A-dependent pathophysiological mechanisms and biomarkers involved in the natural course of cognition in children with Down's syndrome.

During a consultation in their usual care department, dedicated to the care of children with trisomy 21, the children with trisomy 21 and their parents present will be informed about the study. An additional 2 mL of blood (from a blood sample taken as part of the consultation) will be drawn for the study by experienced nurses as part of their usual care. Plasma from this remaining volume will be fixed and analyzed to determine a phosphoproteomic profile. Multidimensional liquid chromatography with ultra-high resolution mass spectrometry will be used to analyze the native proteome and to obtain expression and phosphorylation levels of plasma proteins. Similar procedure will be performed on remaining blood samples of boys without genetic abnormality having blood analysis. Phosphoproteomic profiles of children with Down Syndrome and children without genetic abnormality will be compared to identify specific biomarkers of Down Syndrome.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Down Syndrome

Interventions

Eligibility

Sex: MALEMin age: 6 YearsMax age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Clinical diagnosis of free and homogeneous trisomy 21, * Body mass index (BMI): 15-25, * Able to understand the study based on the pictorial information leaflet and give agreement/assent to participate, * Parent present on the day of the visit to validate their child's consent/assent, if applicable. Exclusion Criteria: * Celiac disease, * Autoimmune dysthyroidism, * Type I autoimmune diabetes, * Alopecia, * Other autoimmune diseases, * Current infectious pathology, * History of infantile spasms, * Autism spectrum disorders, * Epilepsy, * Central nervous system infections, * Leukemia not in remission, * Anti-inflammatory treatments (NSAIDs, local or systemic corticosteroids).

Locations (9)

CHRU de Brest

Brest, France

CHU Grenoble

Grenoble, France

Medilab

La Châtaigneraie, France

Hospices Civils de Lyon

Lyon, France

Medilab

Niort, France

Institut Jérôme Lejeune

Paris, France

Medilab

Parthenay, France

CHU Rennes

Rennes, France

CHU Saint-Etienne

Saint-Etienne, France

Outcomes

Primary Outcomes

Phosphoproteomic profile

The main objective is to determine a phosphoproteomic signature characteristic of the pathophysiological state of trisomy 21. Plasma protein phosphorylation profiles will be analyzed using the Proteas Bioanalytics Inc. platform on blood samples taken from children with trisomy 21, and compared with the phosphorylation profiles of children without trisomy 21 of the same age and sex. Analysis and comparison of trisomy and non-trisomy phosphorylation profiles will reveal a signature characteristic of trisomy 21, potentially reflected by significant differences in plasma protein phosphorylation levels (some of which may be of cerebral origin).

Time frame: 6 months

Secondary Outcomes

Identification of brain proteins

To determine whether the phosphoproteomic profiles characteristic of trisomy 21 make it possible to identify brain proteins (exosomes),

Time frame: 6 months

Impact of environnement on phosphoproteomic profile

To determine whether the differences potentially observed between the phosphoproteomic profiles of children with and without trisomy 21 correlate with the biological and socio-epidemiological data of children with trisomy 21,

Time frame: 6 months

Impact of DYRK1A on Down Syndrome specific proteomic profile

Determine whether the differences potentially observed between the phosphoproteomic profiles of children with and without trisomy 21 are correlated with the level of DYRK1A expression,

Time frame: 6 months