People with Down syndrome have an extra copy of chromosome 21.

Our grantees at Stanford have found that a gene they first identified while studying the origin of some cancers may also play a role in Down syndrome.

This gene, called Usp16, appears to accelerate how quickly stem cells are used up throughout the body, including in the brain. Most of us have just two copies of the gene, but people with Down syndrome have an extra copy of chromosome 21 and therefore an extra copy of this stem cell accelerator gene.

The scientists say that the finding might explain why people with Down syndrome age more quickly and develop Alzheimer’s disease at an earlier age than other people: the stem cells that would normally replenish and repair the body peter out earlier. The work was published in Nature online on September 11.

In a press release from Stanford, senior author Michael Clarke points out that stem cell function is critical for human health:

“This gene is clearly regulating processes that are central to aging in mice and humans and stem cells are severely compromised. Reducing Usp16 expression gives an unambiguous rescue at the stem cell level. The fact that it’s also involved in this human disorder highlights how critical stem cells are to our well-being.”

Clarke, along with scientists from across Stanford and one CIRM Bridges intern, tested the effects of this gene in both mice that mimic the disease and in human cells.

They first grew brain stem cells from mice with an extra copy of Usp16 in a lab dish. Those cells were not able to grow and divide normally. When the scientists reduced the amount of the protein made by Usp16 those cells started to behave more normally in the dish.

Then they did the same experiment with stem cells taken from people with Down syndrome. Reducing the activity of Usp16 in those stem cells made the cells behave more normally in a lab dish. These findings suggest that reducing Usp16 in people with the disease could help their stem cells function more normally and treat some symptoms.

Bloomberg quoted Clarke saying that this discovery could lead to a drug to treat the stem cell defects in people with Down syndrome:

“Like most regulators and stem cell functions, understanding how those things work has potential implications in a wide range of diseases. Now that we have a pathway, there might be drugs that could be used to improve some of the problems.”

The authors are careful to point out that Usp16 is unlikely to be the only factor involved in Down syndrome. However, a therapy targeting this gene could reduce some of the disorder’s debilitating symptoms. 

Amy Adams