Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target
Carolyn B. Smith, PhD
Principal Investigator
Rachel Sare, PhD
FRAXA Fellow
National Institute of Mental Health
Bethesda, MD
2016-2018 Grant Funding: $90,000
Summary
Sleep abnormalities are common among people who have Fragile X syndrome. This team studied sleep issues, aiming to find ways to normalize sleep patterns and - hopefully - also other symptoms of the disorder.
The Results
The team showed that mice with FXS sleep less overall, have more fragmented rest, and spend less time in deep (non-REM) sleep—issues that are especially noticeable in males and seem linked to problems like hyperactivity.
In a 2017 study, they laid the groundwork by documenting these sleep deficits. In 2018 they reported that a drug targeting protein production (rapamycin) actually made some behaviors worse in FXS mice, highlighting the need for careful therapy approaches.
Then, in 2022 papers, they showed that limiting sleep during development causes lasting social and activity issues, while sleep-promoting drugs can partially fix sleep patterns and ease hyperactivity. Together, their findings suggest improving sleep could be a helpful way to support people with Fragile X.
The Science
We hypothesize that sleep abnormalities contribute to behavioral abnormalities in Fragile X syndrome, and we propose that treatment strategies should include a focus on normalizing sleep patterns. Our long-term goal is to identify potentially modifiable risk factors contributing to symptoms of FXS. Our objective is to determine the extent to which social behavior abnormalities, hyperactivity, and learning impairments are improved when sleep is improved in a mouse model of FXS. If improving sleep improves behavior, we propose that treatment of sleep may be a novel therapy for FXS that may be used alone or in combination with other proposed therapies.
Grant Post Revisions
- 2022/12 - Added The Results.
- 2016/06 - Original grant post published.