Hope in the Making: Heidelberg Research Team Shares Key Updates in Schaaf-Yang Syndrome

In a recent research update video from the United in Hope 2025 Conference, scientists from Heidelberg University—Dr. Rachel Gilmore, Dr. Ferdinand Althammer, Felix Franke, and Tim Schubert—shared exciting progress from their FPWR-funded studies focused on Schaaf-Yang syndrome (SYS) and the MAGEL2 gene.

Their work represents an important step forward in understanding the root biological mechanisms behind SYS and exploring promising paths toward targeted therapies.

Understanding the SYS Phenotype and MAGEL2 Function

Tim Schubert began by outlining common traits observed in individuals with SYS as they grow, alongside key genetic and molecular characteristics of the condition. He introduced a helpful visual comparing normal MAGEL2 protein function to that of the altered protein found in SYS.

To further explore MAGEL2’s role, the team is working with a combination of:

• Cell cultures

• MAGEL2 deletion mice

• MAGEL2Pmut rats (engineered to produce an altered MAGEL2 protein)

Together, these tools allow researchers to study the effects of MAGEL2 mutations more accurately—and in ways that closely reflect the human experience of SYS.

Schubert also discussed the potential for oxytocin replacement therapy. In some cases, oxytocin—a hormone involved in social behavior and bonding—may be trapped within cells. Exploring whether releasing or replacing this hormone could improve symptoms is one of the team’s ongoing efforts.

Introducing the SYS Rat Model

Felix Franke shared updates on the new MAGEL2Pmut rat model, a major step forward in SYS research. These rats show key characteristics similar to those seen in humans with SYS, including:

• Delayed weight gain
• Feeding challenges
• Communication difficulties

This model is helping the team explore where and when MAGEL2 is active during development—particularly in brain areas that control hormone production, feeding behavior, and social interactions. It also opens the door to testing how new therapies, like oxytocin, might impact those traits.

Exploring Antisense Oligonucleotide (ASO) Therapies

Dr. Rachel Gilmore is leading work investigating antisense oligonucleotides (ASOs) in the SYS rat model. ASOs are small molecules that can block faulty genetic messages from being made into proteins. They’ve already been used to treat genetic disorders like Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD).

The team’s hypothesis: If the body can stop producing the harmful MAGEL2 protein, could symptoms improve?

While this line of research is still early-stage, it’s raising essential questions:

• Could ASOs alone reduce symptoms?
• What kind of improvements would we expect to see?
• At what age would treatment be most effective?
• Would children and adults respond similarly?
• How often would treatment be needed?
• What side effects might we need to consider?

How You Can Contribute

Dr. Ferdinand Althammer is currently studying oxytocin levels in individuals with SYS. By contributing a saliva sample, families can directly support this important research. Samples are being collected by CombinedBrain on the team’s behalf. Every contribution helps move the science forward.

What’s Next?

This body of work is building the foundation for larger-scale initiatives like GeneSYS, a project designed to test innovative therapies—such as ASOs—that could potentially block the toxic effects of the altered MAGEL2 protein.

It’s early, but it’s promising—and it wouldn’t be possible without the combined efforts of scientists, families, and supporters in the SYS community.

Watch the Full Research Update

Want to hear the full update directly from the Heidelberg research team? Watch the video below, then click here to help fund more breakthroughs for SYS.