A hand holds a stack of speech bubbles.
Cultivating connection: Open communication and data-sharing helps build trust with families engaged in clinical trial research.
Illustration by Olena Koliesnik / Anya Sahni

Leveraging the power of community to strengthen clinical trials for rare genetic syndromes

Families can become not only participants but champions of these research efforts.

In late January 2024, my colleagues and I received startling news. A first-of-its-kind randomized clinical trial testing a potential therapeutic drug for dup15q syndrome was coming to an abrupt end. We had spent nearly 10 years working on this project to help children with this rare neurodevelopmental condition and were not anticipating its untimely termination.

According to Roche Pharmaceuticals, which had sponsored the trial, “the decision to stop was not tied to a prediction of any data, but rather to considerations around company prioritization and opportunities, strategic fit, and other factors.”

Perhaps we should not have been surprised. Only six months earlier, in July 2023, Roche had suspended testing of an antisense oligonucleotide therapy for Angelman syndrome, another rare neurodevelopmental condition, just as the team was preparing for a phase 3 efficacy trial. But my colleagues and I had believed that our dup15q syndrome work, buoyed by a decade of science, advocacy and clinical investment, would be protected.

In response to the trial’s termination, our community of clinicians, researchers and families faced two paths: one of despondency and defeat or one of resiliency and resolve. We wholeheartedly chose the latter. In the weeks that followed, the families we had engaged in this process came forward as extraordinary advocates of our cause.

Together we are still rallying to find a new way forward through new sponsors for the trial. As we do so, I am especially struck by our partnerships with families. The parents and caregivers with whom we have worked are not only consenting participants but true champions of this initiative. Our efforts therefore offer lessons to other research groups seeking to engage with patients and families from a place of shared goals, mutual respect and true collaboration. We have learned that building strong ties with patients and families is essential for researchers working on rare conditions to push their scientific goals forward.

Dup15q syndrome is strongly associated with neurodevelopmental conditions, particularly autism, intellectual disability, motor impairment and epilepsy. It is caused by a duplication on chromosome 15, and the duplicated region contains the UBE3A gene, which is critical for healthy neuronal function, along with several GABAA receptor genes that contribute to GABA (inhibitory) neurotransmission.


o date, treatments for dup15q syndrome, as with many other genetic conditions, have addressed only co-occurring symptoms. None have targeted the genetic etiology or, as a result, the condition’s core neurodevelopmental characteristics.

Unfortunately, in recent years, even when targeted therapeutics are developed, many clinical trials for genetic neurodevelopmental conditions have failed. The main obstacles to success have included an inability to identify biomarkers of drug target engagement, to define evidence-based endpoints that are sensitive to change, and to engage enough families to ensure adequate enrollment.

In that context, our group, in collaboration with clinicians, scientists and families around the world, had been committed to building clinical trial readiness and avoiding such roadblocks for dup15q syndrome. We partnered directly with the Dup15q Alliance patient advocacy group and Roche Pharmaceuticals, as they had a promising GABAA Negative Allosteric Modulator (GABAA NAM), to proactively address our trial readiness goals.

Number ninety: At the Dup15q Alliance International Family Conference in 2023, attendees learned about the effort to recruit 90 participants for the first-of-its-kind clinical trial for a potential therapeutic for dup15q syndrome.
Courtesy of Shafali Jeste

Our efforts included the characterization and quantification of an EEG biomarker and large-scale testing of clinical measures for endpoints sensitive to individual variability, ability and change. The Dup15q Alliance worked with an outside firm to develop a patient-centered “disease concept model,” a framework that categorizes and outlines the major areas of concern for caregivers of people with dup15q syndrome. Such models are being developed across genetic conditions to guide therapeutic targets and are of particular interest to the U.S. Food and Drug Administration.


erhaps most importantly, we built a strong foundation of trust with families. We used several strategies to that end. We sought to engage and empower them by sharing the biomarker and clinical data as it was collected. We also provided them with concrete information about clinical trial participation, through enhanced website content, social media live sessions and Dup15q-Alliance-sponsored webinars. To destigmatize trial participation, we directly addressed our families’ concerns around placebos and safety monitoring, as well as implications for co-occurring interventions. The Dup15q Alliance also developed a centralized recruitment and enrollment process to ensure that any interested family could be connected to the most convenient and appropriate site.

As the GABAA NAM became available for repurposing for this rare condition, we worked directly with Roche to design the trial. I felt bolstered by the partnerships we had forged between industry and stakeholders, and by decisions made that were grounded in experience, patient perspectives and objective data.

Our efforts culminated in the July 2023 Dup15q Alliance International Family Conference. One parent described attending the conference in Nashville, writing: “I will never forget walking into the meeting room and seeing hundreds of families under one roof. Then the keynote speaker gave an unbelievably moving speech centered around hope, while blue bracelets were passed around with the word ‘Believe.’ The speech ended with the number 90 on the screen.” That number represented the recruitment target for our trial.

Energized, the parents in attendance embraced and repeated this message, spreading the word to help us meet that goal. Within a few months, the trial had launched in two sites: the Children’s Hospital Los Angeles and Rush University Medical Center in Chicago.

Within two months, four children were enrolled, including a 10-year-old boy who was among the first patients I had ever diagnosed with dup15q syndrome. Belief and hope infused this community for the remainder of the year. We made plans to open at least three more sites and had more than 20 children on the waitlist for our first wave of participants.


e were so proud to begin realizing a precision health vision for this genetic neurodevelopmental condition. I personally felt validated in my persistent message to families that genetic testing did not simply represent an academic exercise to understand etiology. Rather, such testing could result in making connections across the parent community, better characterizing clinical needs and trajectories, and ultimately offering hope for evidence-based interventions that could improve meaningful outcomes.

When the somewhat unthinkable, albeit not unprecedented, decision was made to halt the trial, our families did not retreat. Within a week, parent after parent sent letters to the leadership of the company, advocating for the trial. They posted videos on social media with beautiful clips of their children with dup15q syndrome, asking the company to reconsider its decision.

One parent wrote that “the dup15q population is small but incredibly mighty,” and shared in a post how their family had raised $25,000 for the cause, moved by the challenges of their 17-month-old child. “The need is here. The funding is here. The participation is here. This community is where the advancements are to be made. I ask that this decision be reevaluated from the lens of the children just coming into their dup15q diagnosis. This could mean higher quality of life for the most vulnerable of populations.”

I believe that any obstacle introduces opportunities for self-reflection, modification and growth. This experience proves no exception. Precision health is no longer an elusive ideal but a tangible reality. Genetic testing is the clinical standard of care for children with rare neurodevelopmental conditions. Disease-modifying therapies will become only more available to test over time. To prepare for this future, many steps are needed, including addressing the current regulatory and funding landscape and de-risking rare disease clinical trials.

This experience has ignited stakeholder deliberation on ways to consolidate the efforts of individual rare neurodevelopmental condition groups into one unified advocacy voice for precision health and clinical trial success. And it has underscored the lesson that families are waiting and eager to be our partners. It is our responsibility, as those that care deeply for these children, to effectively deliver treatments and, in turn, hope.

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