New Study funded! Do CASK changes make human brain cells less active, and can we safely boost that activity again?

Targeting Postsynaptic Defects in CASK Disease by the University of Southampton

Children with CASK disorders face challenges because their brain cells do not communicate as well as they should. Although scientists know that the CASK gene is important for healthy brain development, we still don’t fully understand how CASK changes affect the way brain cells send signals, or which parts of this signalling system might be fixable.

This new study focuses on a key question: Do CASK changes make human brain cells less active, and can we safely boost that activity again?

What the researchers will do

The team will grow human brain cells in the lab and measure how well they “talk” to each other. They will look at:

• How active the cells are at rest
• How they respond when encouraged to fire more, using gentle light-based stimulation
• Whether a specific signalling protein called GluN2B can help restore activity when it is added back into cells that have CASK changes

GluN2B is important because it helps brain cells strengthen their connections — something children need for learning, memory, and development.

The researchers will also test medicines that block GluN2B to confirm whether this protein is truly involved in the communication problems they see. This helps make sure the results are reliable and not caused by something else.

Why this matters for families

This project will not create a treatment right away, but it answers a crucial question that must come first: Is GluN2B a good target for future therapies in CASK disorders?

If boosting GluN2B improves brain-cell activity in the lab, it could guide the development of:

• gene therapies
• medicines that strengthen brain-cell communication
• new approaches to support learning and development

Even if GluN2B does not fix the problem, the results will still help researchers rule out the wrong pathways and focus on the right ones — saving time and accelerating progress.

Why we chose to fund this project

• It uses human neurones, which makes the findings more relevant to children with CASK.
• It studies real CASK variants, including ones found in patients.
• It directly tests whether brain-cell activity can be restored, which is essential for future treatments.
• It offers excellent value, using equipment and methods already available in the lab.
• It fills a major gap in CASK research: understanding how CASK changes affect human brain-cell communication.

Find out more about the research we fund.