Down Syndrome
Conditions
Keywords
Down Syndrome, Typically Developing Participants, Children, Adolescents, Adults
Brief summary
The overall goal of this study is to evaluate biomarkers of oxidative stress, mitochondrial function, and DNA methylation (epigenetics) in order to determine the extent to which these biomarkers are related to cognitive, behavioral and adaptive function in Down Syndrome. The inter-relationship between measurable biomarkers and functional/cognitive abilities will move beyond genetics to provide unprecedented new knowledge and a broader understanding of the underlying pathophysiology and abnormal gene expression induced by trisomy 21.
Detailed description
The Investigators preliminary evidence indicates that people with DS have metabolic biomarkers associated with oxidative stress (GSH/GSSG) and reduced methylation capacity (SAM/SAH) as well as abnormal DNA methylation (epigenetics). The investigative team hypothesize that these abnormal metabolic processes contribute to abnormalities in behavior and development associated with trisomy 21; this connection has never been investigated. Confirming and expanding on the preliminary data would provide new understanding of the biological and functional etiology of the behavioral and developmental delays associated with Trisomy 21. Further, establishing the underlying relationship between metabolic abnormalities and behavioral/cognitive function over the age spectrum can provide strong support for the design of future treatments of individuals with DS aimed at improving their behavior and development. In addition, these biomarkers may also prove to be predictive biomarkers for the risk of developing ASD like behaviors or Alzheimer's disease in this population. Finally, examining the modulating role of diet in the severity of biological abnormalities will provide new information for lifestyle guidance to improve biomarkers and potentially minimize the medical co-morbidities associated with trisomy 21.
Interventions
There is no other intervention, only clinical treatment.
Sponsors
Down Syndrome Research Foundation
Arkansas Children Research Institute
University of Arkansas
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1\. Participant or guardian ability to consent/assent and willing to comply with protocol requirements
Exclusion criteria
1. Trisomy translocation or mosaics. 2. Untreated hypothyroidism 3. Known history of liver disease, renal disease, Hepatitis B or C or HIV 4. Recent infection with fever or requiring hospitalization within past 30 days. 5. Any medical condition, use of medications, nutrient or herbal supplements that would interfere with the study results as determined by the PI 6. Chemotherapy 7. Recent surgery (within 2 months) 8. Untreated Epilepsy 9. Any chronic medical/behavioral condition and/or treatments that may interfere with study related outcomes, as determined by PI 10. Dementia 11. History of a significant adverse reaction to a prior blood draw 12. Any other historical event/information that may, in the opinion of the PI, be a reason to exclude the child from participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Analysis | 2 years | Stool will be collected for Microbiome Analysis on cases and controls |
| Mitochondrial Function Analysis | 2 years | The Seahorse XR extracellular flux analyzer will be used to measure mitochondrial function in cases and controls |
| Oxidative Stress Analysis | 2 years | Thiol measurements will be collected and analyzed between cases and controls |
| Immune Function | 2 years | Salivary measurements of cytokines will be collected on cases and controls |
| Metabolomics | 2 years | Urine will be collected for metabolomics analysis on cases and controls |
| Epigenetics | 2 years | Epigenetics will be evaluated on cases and controls |
| Folate Receptor Alpha Autoantibody (FRAA) | 2 years | Serum will be collected for FRAA analysis on cases and controls |
| Thyroid Function | 2 years | Thyroid measures of Thyroid Stimulating Hormone (TSH), T3, Reverse T3 and free and total T4 will be evaluated on cases and controls |
| Diet | 2 years | Examine the modulating role of diet in the severity of biological abnormalities will provide new information for lifestyle guidance to improve biomarkers and potentially minimize the medical co-morbidities associated with trisomy 21. Dietary contributions will be evaluated on cases and controls |
Outcome results
None listed