Building Momentum: Insights from the KCNQ2 Research Roundtable

At this year’s KCNQ2 Cure Alliance Family and Professional Summit, Drs. Brooke Babineau and Alfred George brought together leaders from the scientific, clinical, and patient advocacy communities for a Research Roundtable. The goal was to shed light on emerging discoveries in KCNQ2-related disorders while underscoring the ongoing challenges in identifying effective treatments. We left the roundtable with an encouraging view of the progress achieved so far and a clear sense of the important work that lies ahead.

The agenda was organized around three key themes, during which researchers, clinicians, and industry professionals shared their work. To encourage a cross-disciplinary dialogue, participants also engaged in a Strategic Working Session aimed at recognizing gaps in KCNQ2 therapeutic development and finding solutions to move the field forward. This blog post summarizes these conversations.

Model Systems

The roundtable began with Dr. Anastasios Tzingounis, who provided an overview of the current state of genetic mouse lines, emphasizing how having representation across the spectrum of KCNQ2 variants has advanced understanding of the biological mechanisms driving different phenotypes. Building on this, Dr. Laurent Villard presented his work with a variant-specific mouse model of KCNQ2-DEE, demonstrating that seizure activity and cognitive outcomes improved in animals treated with Carbamazepine, an antiseizure medication that blocks the flow of sodium ions. 

Shifting to cellular models, Dr. Dina Simkin used neurons generated from patient tissue samples to show how different mutations in the KCNQ2 gene affect the signaling of brain cells. She utilized these data to predict responses to therapeutic treatment. Dr. Zonnekein and Nina Dirkx presented complementary research looking at the short- and long-term effects of different mutations, specifically evaluating excitatory neurons, the cells in which overactivity can lead to seizures. 

Clinical Trial Readiness

In the following session, Dr. Stéphane Auvin opened with a discussion on the importance of selecting the right endpoints for clinical trials. Gabrielle Conecker and Dr. Natasha Ludwig expanded on this, sharing what they have accomplished with the Inchstone Project. Their work aims to shift clinical trial design toward endpoints that capture small but meaningful behavioral changes and to validate tools that can measure them. 

The significance of this work for the KCNQ2 community was underscored by Dr. Michele Postashman, who shared findings from a disease concept model developed by Biohaven for KCNQ2-DEE. By surveying families with lived experience, the project identified that non-seizure outcomes, such as communication, motor skills, and behavioral disorders, are important to track in clinical trials. Dr. Mathieu Milh then presented encouraging data, bringing these family-identified priorities into focus in a clinical setting. His work evaluating the early use of sodium channel blockers in children with KCNQ2 variants showed improvements not only in seizure severity but also in developmental outcomes.

Therapeutic Development

While there are currently no clinical trials specifically for KCNQ2-related disorders, drugs in development for other conditions may offer potential avenues for future research. We heard from Dr. Emma Bowden from QurAlis, who shared information about their clinical trial using a KV7.2/7.3 ion channel opener to treat ALS, epilepsy, and pain. This was followed by Dr. Maurizio Tagliatatela, who discussed his efforts to identify existing drugs that target the KV7.2 channel so they can be repurposed to treat KCNQ2-related disorders. A compound developed by Johnson and Johnson and previously tested in humans showed strong activity in cellular models of KCNQ2-related disease. Dr. Tagliatatela’s team is actively pursuing access to the compound for potential use in KCNQ2-DEE patients. 

Several talks also centered on antisense oligonucleotide (ASO) therapies, a type of genetic medicine that works by modifying protein production at the RNA level. Drs. Andreas Brunklaus and Yuri Maricich shared their experiences utilizing ASOs for Dravet syndrome and SYNGAP-related disorders, demonstrating that these therapies can be safe and effective in children with genetic epilepsies. We then heard from Branden Wheeler of Asymptote, who is applying a genetic medicine approach to KCNQ2-related disorders, showing encouraging results in animal studies.  

Strategic Working Session

During the working session, those present at the Research Roundtable identified several key areas for improvement. A common theme was the need for knowledge sharing and centralization of information. Clinicians highlighted the value of a genetic variant registry, while translational researchers emphasized the importance of a data repository to aggregate published findings. Participants also determined there was a need to amplify family voices through the expansion of natural history studies, which would, in turn, help establish meaningful clinical endpoints (another identified gap). The teams were then tasked with devising strategies to address these issues. By clarifying priorities and identifying actionable next steps, the group created a strong roadmap to advance our understanding and treatment of KCNQ2-related disorders.

The conversations and collaborations that began at the Research Roundtable did not end there. Many of these themes were carried directly into the Family Summit, where families, clinicians, researchers, and industry partners came together to build on these ideas and chart the next steps for our community. You can read more about the Family Summit in this overview.