2025 Year In Review – SAP Chair Message

March 2026

Dear Friends and Supporters,

At the SMSRF, our research strategy is built around one goal: turning strong science into meaningful impact for individuals living with SMS and their families. Because SMS biology is complex, and because families deserve progress that is both real and durable, we focus on supporting work that is scientifically rigorous, strategically chosen, and aligned with a clear long-term path toward therapies.

A key part of how we do this is through the guidance of our Scientific Advisory Panel (SAP). The SAP brings together leading clinicians and researchers across genetics, neuroscience, translational biology, and therapeutic development to evaluate proposals, stress-test assumptions, and help us focus on the work most likely to move the field forward.

This year, we strengthened the SAP by welcoming a new member, Dr. Davut Pehlivan. We are excited to have Davut’s clinician-scientist background and his experience both treating individuals with RAI1-related disorders and studying their underlying biology. That combination, seeing the real-world clinical challenges while also driving research, helps sharpen our priorities and keeps our strategy grounded in what will matter most to families over time.

In 2025, we continued supporting our research portfolio, including work spanning collaborations between groups at McGill University and Stanford University, as we push toward deeper mechanistic understanding and stronger translational foundations. We are especially happy to see groundbreaking research published by the Huang lab at McGill. In a major 2025 study, the team developed new human stem-cell-based SMS models, including 3D cortical brain organoids and SMS neurons grown in the lab. Organoids are tiny, simplified brain-like tissues grown from stem cells that carry the SMS deletion. This is an important step forward because it gives researchers a human system to study early brain development in SMS and a practical platform to test ideas and potential treatments, especially in areas where mouse models may not capture the full picture. Using these organoids and neurons, the researchers found that the SMS deletion can disrupt the normal control mechanisms that help developing brain cells turn genes on and off at the right time. They also showed that SMS neurons can become overly excitable and fire too easily, which may help explain some neurological features seen in patients. The big picture is that these human models help connect the genetic change in SMS to what happens in developing brain cells, and they give the field better tools to measure whether a future therapy is truly making things more normal.

Looking ahead, we see both an opportunity and a responsibility to move on two tracks at once: deepen the fundamental science that explains SMS biology from molecules to brain systems, while also strengthening the translational path by supporting work that de-risks approaches and moves them closer to clinical readiness through robust models, reproducible measures, and therapy concepts that can be advanced with partners. To that end, we have a very interesting new project in the works, and we expect to share more details later this year.

All in all, the progress we are making is not abstract. It is the direct result of a community investing in rigorous science, guided by experts, with the shared belief that SMS can be better understood and treated. We are deeply grateful to every family, donor, volunteer, and partner who makes this work possible.

Filip Sebesta, Chair
SMSRF Scientific Advisory Panel
Board of Directors