Updates from the Director of Scientific & Clinical Initiatives
June 2026
The Office of Management and Budget (OMB) has proposed significant changes to the federal regulations determining how federal research grants are awarded and managed. These changes could make it more difficult to conduct long-term collaborative research that rare disease groups depend on. The proposal could create uncertainty for research funding and limit activities that are essential to scientific progress. For families affected by Dup15q syndrome, every advancement toward better treatments relies on stable funding opportunities, collaboration among researchers, and the ability to share scientific discoveries.
Although Congress does not vote directly on this proposal, your representatives can advocate by communicating potential issues with the OMB before the deadline of July 13. If you do not support the proposed changes, I encourage you to personalize the attached template letter with your family’s story and send it to your Representative and Senators. Additionally, you can directly comment on the proposed changes, and it is imperative to have as many comments as possible for any future amendments to the proposal.
Science is not political, and threats to rare disease research impact our families everywhere. Personal stories are powerful, and our voices can help ensure policymakers understand the impact that OMB’s proposed changes could have for individuals and families living with Dup15q syndrome.
-Dylan Ritter
LEARN
Prucalopride in a Dup15q Mouse Model
Earlier this year, a pre-print looking at prucalopride (Motegrity) to alleviate constipation in a Dup15q mouse model was released. Earlier this month, that paper was officially revised, edited, and accepted for publication! Prucalopride acts through serotonin pathways which are very important for gastrointestinal function. Even if serotonin genes are not duplicated in Dup15q syndrome, addressing serotonin systems in the gut is a specific way to hopefully improve gastrointestinal function in Dup15q syndrome.
Using a Dup15q mouse model that includes a large duplication of many Dup15q genes, researchers tested if prucalopride would improve transit time in the gut as a measure of GI motility. They found that the Dup15q mouse model showed constipation-like symptoms, and that prucalopride improved GI transit time. Additionally, the prucalopride-treated group had lower levels of fecal corticosterone, suggesting lower stress after treatment with prucalopride. Lastly, social contact duration for Dup15q mice improved after prucalopride treatment. Together, these findings suggest that GI dysmotility and constipation-like phenotypes observed in a mouse model of Dup15q syndrome could be improved using prucalopride, and improved GI motility could also potentially improve stress and social behaviors in mice. This is the first study showing GI dysmotility in a mouse model of Dup15q syndrome which creates opportunities for future testing of other drugs.
TREAT
EEG Beta Power in Dup15q Syndrome
Beta power is a way to measure how active the brain is when it is awake and thinking. EEGs are used by researchers to measure tiny electrical signals from the brain, and beta waves are one type of those signals. In Dup15q, many research studies have found that the extra beta power likely comes from excess GABAA receptor activity, which could come from the GABAA receptor subunits duplicated in Dup15q syndrome (read more in last month’s SCI Spotlight).
A recent study from Dup15q researchers looked closer at how the EEG beta power signature correlates to Dup15q symptom severity. Using a new way to compare EEGs between individuals (LRPβ), the researchers found that changes to LRPβ correlate with overall clinical severity in several different areas including language, social, motor domains, and nonverbal cognition. The results were easier to correlate in participants that did not have epilepsy, suggesting that participants with epilepsy may have other confounding genetic contributions that make changes harder to see. Importantly, this study does not tell us how a clinical trial like Basmisanil should work. The study adds background context to how GABAA receptors contribute to a biomarker of Dup15q syndrome, which does add rationale to why a clinical trial should be performed.
The results of this study continue to emphasize EEG beta power as a useful biomarker in Dup15q syndrome. This biomarker, a measurable characteristic of the body that indicates what is happening internally, is being considered as the primary outcome in Newleos’ upcoming clinical trial. A change in EEG beta power would be evidence that Newleos’ Basmisanil drug is interacting and impacting GABAA receptors in trial participants. That clinical trial will start to determine if changing GABAA receptor activity changes any of the symptoms that correlate with EEG beta power in Dup15q syndrome. Â
CURE
Basmisanil Clinical Trial Q&A
As you noticed during the Big Give, Newleos announced that they plan to pursue a Dup15q clinical trial for Basmisanil! On June 16, I hosted a Live Q&A session related to Basmisanil to answer questions the Dup15q community had about the announcement. This session was recorded as a resource for the wider community who could not attend. I have also developed a list of some FAQs that I have collected from the community over the last month since the initial trial announcement. Some of the questions do not have finalized answers, but we are speaking with Newleos now to have them host a Q&A with families once all the trial details are finalized!
If you haven’t seen the original announcement from Newleos, I encourage you to watch a replay of the Newleos team’s presentation from the Big Give.
