Dr. Espinosa explains the interaction between interferon activation and Down syndrome
Dr. Espinosa explains the interaction between interferon activation and Down syndrome | Global Down Syndrome Foundation

Down syndrome mystery solved

Scientists may be one step closer to understanding the mechanisms behind Down syndrome, according to a study published in eLife.

Down syndrome is a genetic condition that results when a person’s cells have three copies of chromosome 21 instead of just two. Scientists call this trisomy 21.  

The study found that cells with trisomy 21 continuously act as though they are fighting an infection even when no infection is present. They release a molecule called interferon, which acts on neighboring cells, activating the immune system and preventing protein synthesis. The synthesis, or creation, of proteins supports all the processes of the body.

“This is transformative because there's almost nothing now about looking at Down syndrome as an immune system disorder,” said Michelle Sie Whitten, co-founder and president of the Global Down Syndrome Foundation, which funded the study and announced the results on Sept. 21

According to the Centers for Disease Control and Prevention, Down syndrome is the most common chromosomal disorder, affecting one in every 700 babies born. Older mothers are more likely to have a baby who has Down syndrome.

“You're born with Down syndrome, but you can live a long, healthy life thanks to advances in medical treatment associated with the co-occurring conditions with Down syndrome,” said Sara Hart Weir, president of the National Down Syndrome Society, an advocacy group that was not involved in the study.

The life expectancy for people with Down syndrome has risen from 10 years in 1960 to about 47 years in 2007.

The idea that interferon response might be linked to Down syndrome is not a new one. In 1980, Dr. Leonard E. Maroun theorized that interferon and trisomy 21 might be linked. In 1998, he published a study in the journal Down Syndrome Research and Practice that presented similarities between the side effects of interferon therapy and the elements of Down syndrome.

With the technology of the time, it was a hard hypothesis to prove. But when Dr. Joaquin Espinosa of the Linda Crnic Institute for Down Syndrome was examining the blood of about 20 people with Down syndrome using modern technology, he noticed that all of them showed constant interferon signaling.

“Clearly, if your immune system is activated 24-7 over a long period of time that must have implications on the person’s body,” Sie Whitten said. “In addition, I think there have been some small studies that have shown that people who have solid tumor cancer who have been on interferon for a long period of time have suffered cognitive deficit.”

In fact, multiple studies over the past 10 years have suggested a link between interferon-based therapies and cognitive symptoms, as well as depression.

According to the National Down Syndrome Society, at least 50 percent of people with Down syndrome also struggle with a major mental health issue such as anxiety or depression.

People with Down syndrome also have a higher incidence rate of endocrine problems, digestion issues, heart defects and Alzheimer’s disease, among other conditions.

“It is true that they're more inclined to get autoimmune diseases and Alzheimer’s,” Sie Whitten said. “They're also extremely protected against other ones: stroke, heart attack.”

Sie Whitten said that learning to understand the mechanisms at work in Down syndrome, why people with Down syndrome are protected from certain diseases and conditions, might help researchers to solve medical questions affecting the general population.

Espinosa has already started the education phase of a project to collect blood samples from 1,000 people with Down syndrome and 500 unaffected people to sequence 10 layers of the blood from each draw. It’s called the Human Trisome Project.

“Looking at blood on a molecular, biological level can lead to many breakthroughs for people with Down syndrome,” Sie Whitten said.  

Dr. Kelly Sullivan, researcher at the Crnic Institute and lead author of the study, has also initiated followup research into interferon response using mice.