A recent publication in the journal of Science Translational Medicine revealed a groundbreaking new approach to a genetic therapy for Dravet syndrome. The new scientific approach was developed and validated through a collaboration between researchers at Allen Institute for Brain Science and University of Washington’s Seattle Children’s Research Institute. The gene therapy was tested in two different mouse models of Dravet syndrome where it was able to reduce premature death as well as decrease the number of spontaneous and heat-induced seizures.
At the end of 2024, DSF, with support from Marlins for Mason, announced funding for a Transformational Science Grant to the group at the Allen Institute to continue their work on this novel genetic therapy. Today’s blog will delve deeper into their progress and future plans, including some insights shared directly from John Mich, PhD, a lead scientist on the project.
Treating Dravet Syndrome at the Cause
The majority of cases of Dravet syndrome are caused by mutations in the SCN1A gene. SCN1A holds the instructions to create a sodium channel called Nav1.1. Every person has two copies of the SCN1A gene; mutations causing Dravet syndrome occur in one copy of the gene, reducing the number of healthy Nav1.1 sodium channels by half, which ultimately causes disruptions to how certain cells in the brain communicate. A genetic therapy could address the cause of Dravet syndrome at the source, potentially modifying the entire course of the disease, but there are several barriers to creating genetic therapies for Dravet syndrome.
Overcoming Traditional Challenges for a Gene Therapy
Ideally, a genetic therapy for Dravet syndrome would replace the faulty gene, but the SCN1A gene is very large, making it difficult to deliver a replacement gene. The current work from the Allen Institute overcomes that challenge by splitting the large gene into two halves, each of which will fit inside the delivery packaging, called a viral vector. Once the two halves of the gene are delivered to a cell, they can be joined to form a full, healthy copy of the SCN1A gene.
Another challenge in the development of a genetic therapy is actually delivering the therapy to the correct cells in the brain. Not only is the central nervous system, which includes the brain, highly protected and difficult to reach, but only a specific subset of neurons uses this particular sodium channel and should be targeted with the therapy. Unique scientific tools had to be developed and tested to ensure this new gene therapy reached the cells that needed it most in the brain.
We asked researcher John Mich, PhD to explain more about what makes this gene therapy approach unique.
Our approach is unique in two ways. First, we use a cell class-specific driver that is functional across mammals so that we can verify its properties in test animals as well as in human patients. Second, we deliver a whole new fresh copy of the gene that is dysfunctional in most Dravet patients (SCN1A), so it is unbeholden by any one particular patient’s exact mutation. These two properties together could enable a Dravet gene therapy to be safer and more effective for the broadest range of patients.
The Path Towards a Therapy for Patients
Developing a genetic therapy can take a long time from start to finish, often longer than a decade. While the results from these studies in mice so far are impressive and provide a lot of promise that this approach might have the potential to translate into a therapy for patients with Dravet syndrome one day, there is still a lot of work to be done to take this from experiments in mice to testing the therapy in human patients. Indeed, more research needs to happen in mouse and cell models to fully understand how this therapy might work best.
We asked Dr. Mich what research questions still need to be explored before this could translate to a new therapy for patients?
There are several important studies that need to be done before it could be tested in people. First, we need to verify exact dosing and formulation and route of administration that can target enough neurons to be effective in people. Additionally, we need to verify that there are no unexpected safety issues that show up when we deliver enough of the therapy under controlled experimental conditions. These are hard experiments that still need to be done, but based on our strong results so far, we have firm belief there is potential for a real treatment option for Dravet patients.
DSF Research Support is Making a Difference
The Dravet Syndrome Foundation, with support from the entire Dravet patient-family community, has been able to direct over $11.3M to Dravet-related research. DSF grants fill a critical gap in enabling new research projects to gather pilot data and sustaining larger research projects to delve deeper into transformational research. At the end of 2024, DSF announced $500,000 in grant funding, with support from Marlins for Mason, for Boaz P. Levi, PhD; Bryan B. Gore, PhD; John K. Mich, PhD; and Tim Jarsky, PhD at the Allen Institute to continue work on this important gene therapy, aiming to understand more about how the therapy works to restore function in the brain and ensuring its effectiveness in models of various types of mutations that lead to Dravet syndrome.
Dr. Mich elaborated on how the recent funding from DSF will help advance this project.
The DSF funding is a great opportunity to understand how whole SCN1A gene delivery can boost the health of the inhibitory neurons, which are dysfunctional in Dravet syndrome, and how that relates to the seizure control we see. At the same time, we will be performing molecular profiling of these ‘rescued’ inhibitory neurons, which could provide biomarkers of diseased and rescued neurons. Finally, we will also fully characterize the rescue potential in missense mouse mutations, which has not been reported previously. All together, these are really important questions that will guide any gene therapy approach for this terrible disease.
Support and advocacy for research from DSF and the community over the last 15 years has spurred immense progress in our understanding, care, and treatment of Dravet syndrome. DSF is proud to fund the important work happening at the Allen Institute and we look forward to hearing more of the exciting progress to come in the years ahead.
Finally, we asked Dr. Mich to share from his perspective as a scientist, how can patients and patient advocates support research in these early-stages?
Early-stage therapy development is inherently expensive, requiring highly controlled experiments and coordinated efforts from teams of scientists and clinicians. To advance our work, significant funding is essential. That said, there’s a lot individuals can do beyond fundraising. Participating in surveys, clinical studies, and genetic profiling contributes valuable data that informs development strategies and trial design.
Patient voices also play a powerful role—when heard, they influence government agencies like the FDA and NIH, as well as investors and scientists themselves, helping keep awareness and funding momentum alive. Much of our progress to date has been made possible by public investment through the NIH, especially the BRAIN Initiative. Continued public and governmental support for science is vital. We believe science is an engine for improving quality of life—both through better health and a stronger economy.
Learn More:
- Check out this coverage of the project from the Allen Institute and Seattle Children’s
- Learn more about DSF’s funding for this project
- Read an overview of progress towards genetic therapies for Dravet syndrome, or learn more about the genetics of Dravet syndrome
- Keep up to date on advocacy initiatives that may relate to funding for science and research
- The original research publication:
Mich JK, Ryu J, Wei AD, Gore BB, Guo R, Bard AM, et al. Interneuron-specific dual-AAV SCN1A gene replacement corrects epileptic phenotypes in mouse models of Dravet syndrome. Sci Transl Med 2025;17. https://doi.org/10.1126/scitranslmed.adn5603.
