Today, World Down Syndrome Day, is an opportunity to spread awareness about Down syndrome in our community and around the globe. The worldwide event is held each year on March 21, in recognition of the fact that people with Down syndrome are born with three copies of chromosome 21 instead of the typical two.
As we celebrate World Down Syndrome Day, we shine a light on work that is elongating lives and improving health outcomes for those with Down syndrome. There is much to take pride in and a dedicated team driving rapid advancements in the field.
Colorado is an established leader in Down syndrome research and care, and it is no exaggeration to say our campus is at the epicenter.
With a robust network of partners spanning the Front Range, we have gone all in over the last 15 years to build a comprehensive medical support system for people with Down syndrome and assemble an unmatched research team.
That team is challenging conventional wisdom about Down syndrome and exploring new avenues with tremendous promise.
These researchers are harnessing historic volumes of data and fostering collaboration to decipher the co-occurring conditions of Down syndrome. They are also making breakthrough discoveries at the intersection of Down syndrome and Alzheimer’s disease with potential benefit for us all.
With their leading-edge clinical studies and research findings, new diagnostic tools and treatments for health conditions that people with Down syndrome face are right around the corner.
Down syndrome occurs when a child is born with an extra copy of chromosome 21. Also known as trisomy 21, the condition affects about 1 in 700 babies born in the U.S. each year and is associated with multifaceted cognitive and physical impacts.
Despite being the most common chromosomal disorder diagnosed in this country, Down syndrome research was severely underfunded until recent years. The landscape has shifted thanks to advocacy and philanthropy, and with an influx of new federal resources, our campus is leading the charge.
In 2008, the Linda Crnic Institute for Down Syndrome was established at the CU School of Medicine, and with it our campus’ leadership as one of the only academic centers fully dedicated to Down syndrome. Two years later, the Anna and John J. Sie Center for Down Syndrome opened its doors at Children’s Hospital Colorado, making comprehensive care available on our campus to children prenatally to age 25.
We can credit one Colorado family as the impetus for both organizations. When Michelle Sie Whitten and Tom Whitten’s daughter, Sophia, was born with Down syndrome, their search for the latest research and evidence-informed care came up lacking. Along with Michelle’s parents, Anna and John Sie, the family gathered leading scientists to explore the possibilities and together began the due diligence needed to create the world’s first academic home for Down syndrome research and medical care.
Thus the Crnic Institute was founded, as was the important affiliate advocacy, education and fundraising organization called the Global Down Syndrome Foundation ‒ the largest nonprofit in the world dedicated to Down syndrome research, led by founder and CEO Michelle Sie Whitten. With our experts, the Sie family’s philanthropic leadership and a shared vision, we were on our way.
"On World Down Syndrome Day, we celebrate many major accomplishments ‒ from creating the largest research and medical care institute for people with Down syndrome, to government advocacy that has led to over $200 million in funding and medical breakthroughs in just five years,” said Michelle Sie Whitten. “The confluence of amazing individuals with Down syndrome and their families, CU’s dedication to our cause, brilliant scientists and medical care professionals and generous donors have all led to this moment.”
The Crnic Institute, which also includes key researchers from the CU Alzheimer’s and Cognition Center, is now the largest geographical cluster of Down syndrome researchers on the planet, comprising 50+ labs across the University of Colorado, 200+ scientists and a strong network of partners. The Sie Center serves over 2,200 pediatric patients from 33 states and 10 countries. And at a new pilot clinic at Denver Health serving adults with Down syndrome, our faculty are fulfilling a substantial unmet need.
Within the last 25 years, the incidence of people with Down syndrome has increased and life expectancy has doubled from 30 to 60 years, leading to unprecedented opportunities to delve deeper into conditions that many experience. That deep dive is the core focus of a supergroup of researchers at the Crnic Institute.
“This is the first time in history that we have a sizable population of adults with Down syndrome receiving proper medical care,” said Crnic Institute Executive Director Joaquin Espinosa, PhD. “So for the first time, we are learning about the co-occurring conditions affecting them. Twenty, 30 years ago, we didn't have these opportunities.”
Since taking the helm of the Crnic Institute in 2017, Espinosa has elevated our work in Down syndrome to ever greater heights. An accomplished cancer researcher and genomicist, he has led with passion and focus. Under his leadership, research at the Crnic Institute has grown, spanning basic science to clinical and translational research and crossing disciplines. Teams there are looking at the mechanisms by which trisomy 21 causes Down syndrome, its neurological and immunological impacts, and safer treatments for associated conditions.
A third copy of chromosome 21 causes a unique disease spectrum. Those with Down syndrome are genetically protected from developing some conditions, like solid tumor cancers and hypertension. But they are strongly predisposed to developing others, including
autoimmune disorders and Alzheimer’s disease.
While the genetic basis of Down syndrome has been known for more than half a century, how the extra copy of chromosome 21 leads to these differences remains unclear.
In 2016, researchers at the Crnic Institute launched the Crnic Institute Human Trisome Project, the first and most in-depth study of its kind, to bring light to these phenomena. This natural history study examines Down syndrome across the lifespan, drawing volumes of data that are helping advance understanding of human health in the context of trisomy 21.
To date, the Human Trisome Project team has amassed more than 22,000 samples from nearly 1,000 participants with and without Down syndrome across the country. Among their results is the discovery that the immune systems of people with Down syndrome are constantly in overdrive, leading to chronic inflammation.
This invaluable data is available to the global scientific community through a National Institutes of Health program called the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Data Coordinating Center, which Espinosa co-leads.
“The INCLUDE Data Hub opens a new frontier in Down syndrome research, in which large-scale datasets are made widely accessible to accelerate discoveries that will benefit people with Down syndrome in their lifetimes,” he said.
Given the immune system’s central role in Down syndrome, several current clinical trials focus on normalizing its function.
Immune-driven skin conditions including alopecia areata and psoriasis are more common in people with Down syndrome. A current trial is testing the use of an immune-modulatory drug for treatment and exploring its broader applications. By targeting immune dysregulation, the study may also uncover potential benefits for health, cognition and quality of life.
The Crnic Institute is also testing therapeutic interventions for a rare, debilitating condition called Down Syndrome Regression Disorder that causes people to decline suddenly, often losing the ability to speak and perform daily activities. With growing evidence pointing to the possibility that the immune system may be attacking the brain, immunotherapies hold promise for treating the disorder.
Every person with Down syndrome has the brain pathology of Alzheimer’s disease by age 30 or 40. While the majority will develop the disease, possibly as many as one-third never do despite having the amyloid deposits that cause Alzheimer’s in their brains.
Huntington Potter, PhD, director of the Alzheimer's Disease Program at the Crnic Institute and director of the CU Alzheimer’s and Cognition Center, is exploring why that is and what we can learn about dementia in typical people by studying people with Down syndrome.
Potter is also looking at ways to boost immune cells in the brain that eat amyloid deposits, using an FDA-approved drug called Leukine, in the hope of preventing harmful buildup in the first place. His lab has established Leukine’s safety and promising results of efficacy in humans with Alzheimer’s disease, and recent findings indicate that this potential treatment for Alzheimer’s may also have important cognitive benefits for people with Down syndrome. Now, his team is recruiting for a study of the drug in young adults with Down syndrome to test its safety and potential ability to improve their cognition.
“We are breaking new ground in studying both of these disorders – Down syndrome and Alzheimer’s disease,” Potter said. “We hope that this therapy will greatly improve quality of life in both populations.”
While just a snapshot of the work taking place in Down syndrome today, these efforts offer reason to celebrate this World Down Syndrome Day.
Ask Espinosa and Potter about their rapid progress, and they point to broad and deep collaboration, and a willingness to work outside the bounds of convention.
“We are here to serve people with Down syndrome, and we will do whatever it takes toward that end,” said Espinosa. “The sky's the limit when we all come together.”