Down Syndrome
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALBlood sample
Recovery of plasma from the bottom of a blood collection tube.
Sponsors
Proteas Bioanalytics
Göteborg University
Perha Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
6 Years to 12 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphoproteomic profile | 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of brain proteins | 6 months | To determine whether the phosphoproteomic profiles characteristic of trisomy 21 make it possible to identify brain proteins (exosomes), |
| Impact of environnement on phosphoproteomic profile | 6 months | 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, |
| Impact of DYRK1A on Down Syndrome specific proteomic profile | 6 months | 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, |
Countries
France
Outcome results
None listed