GO-DS21 will identify and validate new causative mechanisms of comorbidity of obesity and intellectual disability (ID) in Down Syndrome (DS) that could be applicable beyond DS. The project will provide a new paradigm for understanding gene overdosage in comorbidities associated with DS, particularly ID and obesity.

Specific aims:

  • To determine comorbidity patterns and associated factors seen during the early lifetime (before 45 years) in persons with DS
  • To decipher the contribution of environmental factors (such as diet, stress, physical exercise) to DS obesity/ID/anxiety comorbidities
  • To investigate the effects of overdosage of three Hsa21 candidate driver genes to explain comorbid patterns in DS
  • To identify specific physiological biomarkers and epigenetic signatures derived from human samples and rodent models
  • To integrate molecular and clinical data across different spatial and temporal scales of biological complexity using computational biology models and machine learning
  • To design new therapeutic interventions including pharmacological compounds, gene therapy and environmental intervention (controlled diet, exercise and reduced stress) to ameliorate the comorbidities
  • To devise innovative ways for therapeutic intervention to reduce obesity and related comorbidities to improve the lives of people with DS

What is the expected impact of GO-DS21?

  • Novel clinical national and international guidance and innovative therapies
  • Better prevention and diagnosis of obesity and ID for people with DS, their families, and caregivers
  • Newly identified biomarkers to inform accurate and early diagnosis
  • Improved prognosis and enhanced monitoring through clinical and fluid biomarkers
  • Increased visibility the field of DS research
  • Broader impact beyond DS as causative mechanisms of obesity and cognitive impairment
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