Phosphoproteomic Profile of Children With Down Syndrome
- Conditions
- Down Syndrome
- Interventions
- Biological: Blood sample
- Registration Number
- NCT06279208
- Lead Sponsor
- Perha Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 60
- 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.
- 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).
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Children with Down Syndrome Blood sample 30 boys with Down Syndrome, between 6 and 12 years old, coming for a routine car consultation during which blood sampling is scheduled (6 different care dedicated centers). Children without genetic abnormality Blood sample 30 boys without genetic abnormality, between 6 and 12 years old, coming to an analysis laboratory for a blood test (3 different laboratories)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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,
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 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,
Trial Locations
- Locations (7)
CHRU de Brest
🇫🇷Brest, France
CHU Grenoble
🇫🇷Grenoble, France
Medilab
🇫🇷Parthenay, France
Institut Jérôme Lejeune
🇫🇷Paris, France
Hospices Civils de Lyon
🇫🇷Lyon, France
CHU Rennes
🇫🇷Rennes, France
CHU Saint-Etienne
🇫🇷Saint-Etienne, France