Phosphoproteomic Profile of Children With Down Syndrome (PEPS)

Perha Pharmaceuticals

Status: Completed

Conditions: Down Syndrome

Treatments: Biological: Blood sample

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT06279208

2023-A00272-43

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: Male

Ages: 6 to 12 years old

Volunteers: No Healthy Volunteers

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).

Trial design

60 participants in 2 patient groups

Children with Down Syndrome

Description:

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).

Treatment:

Biological: Blood sample

Children without genetic abnormality

Description:

30 boys without genetic abnormality, between 6 and 12 years old, coming to an analysis laboratory for a blood test (3 different laboratories)

Treatment:

Biological: Blood sample