Summary of the 2025 Research Roundtable
This blog post shares key takeaways from the 4th Annual CACNA1A Research Roundtable, where more than 70 experts came together with one shared goal: getting real treatments to our children and loved ones as quickly and safely as possible. The discussions focused on how close CACNA1A research is to moving from the lab into human clinical trials—and what still needs to happen to get there.
A central theme of the meeting was a “multiple shots on goal” approach—pursuing several treatment strategies simultaneously so that every person with CACNA1A has a chance at meaningful therapy. Most importantly, the community is closer than ever to clinical trials. Researchers now have promising methods to measure disease progression, and a variety of treatment approaches, including gene therapies, are advancing. The next two years will be critical as the field prepares for the first major clinical trial for CACNA1A-related disorders, expected to begin in 2026. Please read on to learn more, and if you have any questions about our science strategy or want to learn more about how you can support this work, please don’t hesitate to reach out to us - science@cacna1a.org
The CACNA1A Foundation hosted its 4th Annual CACNA1A Research Roundtable on Monday, November 3, 2025. For the first time, the meeting was held virtually—an adjustment that enabled our largest research gathering to date. The global CACNA1A Research Network brought together 70 researchers, clinicians, industry representatives, and consultants to discuss how to continue advancing research toward clinical trials.
The meeting built on recent progress in therapeutic development for CACNA1A-related disorders, advances made possible in part through Foundation-funded projects. Given the wide spectrum of CACNA1A-related disorders and the range of disease severity, the Foundation’s research strategy continues to focus on pursuing “multiple shots on goal” to achieve the greatest possible impact for the entire community.
The roundtable consisted of two sessions and featured five presentations on the latest CACNA1A research, each followed by a facilitated discussion.
Session 1: Biomarkers and Endpoints for Clinical Trials
Biomarkers are measurable biological traits that help identify or monitor a medical condition. Examples include changes in blood protein levels, specific patterns of brain activity, or responses to defined stimuli. In clinical trials, biomarkers can also serve as endpoints—the measures used to determine whether a therapy is effective. Ideally, an endpoint can be reliably measured before and after treatment. If the wrong endpoint is chosen, a treatment’s true effect may be missed. Currently, there are no validated biomarkers for CACNA1A-related disorders.
Dr. Elisabetta Indelicato, PhD, MD, a clinician-researcher from the University of Innsbruck in Austria, presented preliminary data identifying distinct patterns of brain activity in individuals with CACNA1A-related disorders. These patterns (from EEG recordings) were not observed in individuals without CACNA1A variants or in those with other neurological conditions that share overlapping symptoms. While further work is needed to validate these findings in a larger CACNA1A population, the data suggest a promising potential EEG biomarker for the community.
Kristin Baranano, MD, PhD, Sara Shakin, MD, and Jen Keller, PT, from the Kennedy Krieger Institute (KKI) and Johns Hopkins, focused on outcome measures used in clinical trials. While biomarkers define what is being measured, outcome measures are the tools used to detect change in that endpoint. The KKI team presented data from the CACNA1A Clinical Assessments Research Study (CCARS), which evaluated 23 individuals with CACNA1A-related disorders for ataxia, eye movement abnormalities, balance, and dystonia. Their findings highlighted which clinical assessments may be the most sensitive and reliable for detecting change in future trials.
Key Takeaways from Session 1:
These two presentations represent important milestones in preparing for CACNA1A clinical trials. Data collected across multiple research platforms are beginning to identify possible trial endpoints. An EEG signature could allow researchers to measure whether a therapy restores more typical brain activity after treatment. In addition, baseline data from CCARS—using standard movement disorder assessments such as the Scale for the Assessment and Rating of Ataxia (SARA)—will help determine whether these tools are sensitive enough to detect meaningful change over time.
This progress highlights the power of participation in research and data collection programs. Community involvement enables the collection of critical information needed to advance therapies toward successful clinical trials.
Session 2: Therapeutic Development and Translation to Clinical Trials
Session 2 featured three presentations from researchers developing therapeutic approaches for CACNA1A-related disorders, all with potential to advance toward the clinic. A key challenge discussed was identifying the next steps needed to move these projects from academic laboratories to pharmaceutical partnerships.
Dr. Sam Young, PhD, from UNC, presented an update on his gene-replacement therapy program. His team is using a novel delivery system, an HdAd vector, designed to deliver a healthy copy of the CACNA1A gene into the brain. When injected, the vector activates CACNA1A expression specifically in the cerebellum, where many CACNA1A-related symptoms originate. Dr. Young has demonstrated that CACNA1A can be expressed in the cerebellum of healthy mice and is now optimizing the delivery method to test the therapy in a CACNA1A-deficient mouse model. If this approach improves ataxia in the animal, it will provide important evidence supporting its potential benefit for individuals with CACNA1A-related disorders.
Dr. Henry Colecraft, PhD, from Columbia University, shared progress on his EnDUBs project. EnDUBs are engineered proteins designed to prevent the breakdown of important proteins, such as calcium channels, allowing them to function for longer periods. This approach may benefit individuals with CACNA1A variants who produce reduced amounts of functional protein. Dr. Colecraft has identified EnDUBs that increase Cav2.1 activity and is now working to develop versions that specifically target the alpha-1A subunit.
Dr. Runwei Yang, PhD, from the University of Chicago, presented new data from his project to increase CACNA1A gene expression in the brain. His team developed antisense oligonucleotides (ASOs) that enhance gene expression, leading to increased production of functional Cav2.1 channels. In a CACNA1A-deficient mouse model, boosting gene expression improved both ataxia and behavioral symptoms. Next steps include testing these ASOs in human cell-based systems, including iPSC-derived neurons and brain organoids.
Key Takeaways from Session 2:
These presentations mark significant milestones in the CACNA1A therapeutic pipeline. For the first time, multiple approaches show the potential to modify disease biology. However, additional work is required to advance these programs to Proof-of-Concept and ultimately to IND-enabling studies and clinical trials. Achieving these milestones will require substantial funding over the next 3–5 years—not only for the projects presented, but across the Foundation’s broader research portfolio.
These presentations mark significant milestones in the CACNA1A therapeutic pipeline. For the first time, multiple approaches show real potential to modify disease biology. While meaningful progress has been made, additional work is required to advance these programs to Proof-of-Concept (demonstrating effectiveness in disease models) and ultimately to Investigational New Drug (IND)-enabling studies and clinical trials. Achieving these milestones will require substantial funding over the next 3–5 years—not only for the projects presented, but across the Foundation’s broader research portfolio.
Conclusion
A critical question moving forward is how best to support the next phase of clinical trial readiness and therapeutic development. While the funding landscape has changed and it is no longer feasible to advance every promising project simultaneously, scientific progress must continue—especially as clinical trials approach.
Michael Strupp, MD, shared a preview of IntraBio’s upcoming IB1001 study, which will examine the effects of N-acetyl-leucine in CACNA1A-related disorders and is expected to begin recruiting in fall 2026.
To guide future decisions, the Foundation has launched a Science Strategy Assessment to evaluate its research agenda and convene an expert committee to help prioritize efforts over the next 18–24 months. Community input and support are essential. Your priorities help shape our research strategy, and your support helps move this work forward as we enter an exciting and pivotal new chapter.