Clinical trial NCT06279208: Phosphoproteomic Profile of Children With Down Syndrome
Official title: Exploratory Phosphoproteomic Study to Discover DYRK1A-Dependent Blood Biomarkers in TriSomy 21 Carriers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Down Syndrome
Lead sponsor: Perha Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Proteas Bioanalytics
name: Göteborg University
First posted: 2024-02-28
Enrollment: 60
Sex: MALE
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 30 Children with Down Syndrome and 30 children without genetic abnormality

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Phosphoproteomic profile
timeFrame: 6 months
Secondary outcomes:
measure: Identification of brain proteins
timeFrame: 6 months
measure: Impact of environnement on phosphoproteomic profile
timeFrame: 6 months
measure: Impact of DYRK1A on Down Syndrome specific proteomic profile
timeFrame: 6 months
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU de Brest
city: Grenoble
country: France
facility: CHU Grenoble
city: La Châtaigneraie
country: France
facility: Medilab
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Niort
country: France
facility: Medilab
city: Paris
country: France
facility: Institut Jérôme Lejeune
city: Parthenay
country: France
facility: Medilab
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Etienne
country: France
facility: CHU Saint-Etienne
Study officials:
References: