Fostering Inclusion in Down Syndrome Research

Next Tuesday is World Down Syndrome Day (WDSD). Held annually on the 21st day of the third month (3/21)—signifying the triplication of the 21st chromosome that causes Down syndrome—the observance aims to bring awareness to the most common chromosomal cause of mild-to-moderate intellectual disability.

Research on Down syndrome is a vital part of NICHD’s mission. We have made great progress in supporting and treating people with the condition. The average life expectancy of a person with Down syndrome has increased from 25 years in 1983 to 60 years today. Yet there remains much to do.

The theme for this year’s WDSD observance—With us, not for us—reflects a major goal of the NIH-wide INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) project, which NICHD co-leads. Launched in 2018, INCLUDE aims to increase the participation of people with Down syndrome and their families in clinical research to expand our knowledge about the condition and its links to other health issues, with the ultimate goal of improving the health and quality of life of affected individuals.

With generous congressional funding through INCLUDE, researchers are testing the anti-inflammatory medicine tofacitinib as a treatment for autoimmune skin conditions that are common in people with Down syndrome. The investigators are also monitoring tofacitinib’s potential benefits for cognitive function and quality of life. Preliminary results laid the groundwork to develop a clinical trial comparing tofacitinib with two other medicines for treatment of Down syndrome regression disorder (DSRD). DSRD is a devastating condition in which people with Down syndrome suddenly lose many skills of daily living, such as the ability to feed themselves or use the bathroom. The new study plans to begin recruiting participants by May 2023.

Sleep disorders, which are common among people with Down syndrome, can negatively affect behavior, cognition, learning, memory, and cardiovascular health. Several projects funded through INCLUDE aim to understand and treat obstructive sleep apnea (OSA) in people with Down syndrome. For example, researchers are evaluating a combination of two oral medications as a treatment for OSA in children with Down syndrome. Another study is assessing an implant device that stimulates the nerve that enables tongue movement to treat OSA in adolescents and young adults with Down syndrome. Other researchers are developing a home-based OSA-detection tool, which may offer an alternative to costly tests in a specialized sleep laboratory.

As its name reflects, INCLUDE is committed to expanding and diversifying the pool of clinical research participants and the Down syndrome scientific workforce. As a follow-up to last fall’s Building a Diverse Community for Down Syndrome Research workshop, INCLUDE will be launching a webinar series to foster communication and collaboration with underrepresented groups and promote diversity. Furthermore, several open funding opportunities emphasize diversity, equity, inclusion, and accessibility. These include an initiative to include community perspectives in reducing health disparities in Down syndrome research, an initiative to support small-scale research projects at institutions that do not receive substantial NIH funding, and support for short courses to train the next generation of Down syndrome researchers in state-of-the-art clinical research skills.

Down syndrome is also an important focus for my own research laboratory at the National Human Genome Research Institute. We ultimately aim to develop prenatal therapies to improve cognition in infants with Down syndrome. This work relies heavily on mouse models of the disorder. This week, we published findings that challenge conclusions from decades of work with the Ts65Dn mouse, long considered the “gold standard” in Down syndrome research. We found that this mouse model has exaggerated cognitive traits that do not accurately represent the cognitive symptoms of people with Down syndrome. Our results also suggest that the newer, more genetically accurate Ts66Yah mouse may hold greater promise for work to develop treatments that improve cognition in people with Down syndrome.

Through INCLUDE and other NIH projects, we are laying the groundwork for future Down syndrome research advances. This WDSD, I encourage everyone to learn more about Down syndrome and how people with the condition and their families can become involved in research.