Research Reveals Distinct Oxygen Processing in Down Syndrome

Researchers at the University of Colorado Anschutz Medical Campus’s Linda Crnic Institute of Down Syndrome (Crnic Institute) have published a new study in cell reports that highlights significant variations in the red blood cell and oxygen physiology in people with Down Syndrome. This research is a component of the human Trisome Project, an extensive and comprehensive cohort study of people with Down Syndrome that includes multi-omics datasets, the largest biobank for Down Syndrome research to date, and a through annotation of clinical data.  

Down Syndrome (DS) resulting from trisomy 21 (T21), the most common chromosomal defect that is a major cause of intellectual and developmental impairment. People with DS have benefited from extraordinary improvements in health out comes and expectancy over the past century, mostly due to advancements in medical care and more integration into most facets of society. 

Numerous congenital heart defects (CDHs), autism spectrum disorders, seizure disorders, obstructive sleep apnea (OSA), autoimmune disorders, severe complication from respiratory infections, diverse leukemias and Alzheimer’s disease are among the conditions that this growing population is more likely to experience later in life. Epidemiological studies of this population reveal a unique clinical profile that is characterized by varying risks of co-occurring conditions throughout their lifespan.  

To find physiological variation between research participants with down syndrome and controls from the general community, the Crinc Institute team initially examined hundreds of blood samples. They discovered that a physiological condition akin to hypoxia, or low oxygen, is brought on by triplication of chromosome 21, also known as trisomy 21, the chromosomal defect that cause down syndrome.

Significant alteration in the gene expression that suggest low oxygen availability were defected, such as the stimulation of numerous hypoxia-inducible genes and proteins and elevated amounts of components involved in the creation of heme the oxygen-transporting molecule found inside the red blood cells.  

These findings highlight the importance of hypoxia and hypoxic signaling in discussion about the health of individuals with DS, says Dr. Joaquin Espinosa, one of the paper’s senior authors and executive director of the Crinc Institute. He is also a professor of pharmacology and the principal investigator of the human Trisome Project. The outcomes are outstanding. According to lead author Dr. Micah Donovan, “it is safe to say that blood from people with down syndrome resembles that of someone who was recently flown to a high altitude or who received an injection of erythropoietin (EPO), the master regulator of erythropoiesis, the process of forming new red blood cells.  

The research team at the Crnic Institute is currently organizing many re-examinations, specifically aiming to provide light on the methods to enhance oxygen physiology in the DS community. “Author anticipates that this significant discovery made by our scientists at the Crinc Institute will result in more treatments very soon,” said Michelle Sie Whitten president and CEO of the Global Down Syndrome Foundation, a partner and associate of the Crinc Institute.  

Reference  

Micah G. Donovan et al, Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome, Cell Reports (2024). DOI: 10.1016/j.celrep.2024.114599.