CASK Research

Research

Gene therapies

"The promise of Gene Therapy is that it addresses the fundamental root cause of a disease. But it's still in early stages. There's so much innovation left on the table. You can't rely on yesteryear's technology — you have to constantly be innovating." — Rachel McMinn, PhD — CEO & Founder of Neurogene

Gene therapies are therapeutic approaches that alter the way a gene works, therefore targeting the root cause of genetic diseases. There are several different types of gene therapy.

Gene replacement

This approach adds a working version of the CASK gene into the body to compensate for the faulty one. 👉 Think of it like adding a new instruction manual when the original is damaged.

Will it work for CASK disorders?

Gene replacement has been licenced for other neurological diseases like Spinal Muscular Atrophy (SMA) and AADC deficiency. For CASK disorders, getting the right "dose" will be of vital importance, delivery to the brain is difficult and immune response risks are high. A gene replacement trial for a similar disorder (STXBP1) has been halted following the death of a child in the trial. The CASK community were hopeful that the technology used in this gene therapy would be one it could harness for its own clinical trials. The cause of the death is still unknown.

Gene replacement diagram

X-Chromosome reactivation (females only)

Girls have a "backup" copy of the CASK gene that is switched off. This approach tries to turn that healthy copy back on. 👉 Like switching the power back on to a spare system that was shut down. A very natural approach since it uses the body's natural gene and avoids adding new DNA. It may also maintain natural regulation. This research is still at an early stage and has never been licenced.

Will it work for CASK disorders?

It could be a viable therapeutic but only for females, since males do not have a "back-up" copy of the CASK gene to switch back on. Early work in CASK has shown that it is possible to switch back on the silenced CASK gene in human cells. We are awaiting work to begin on mouse models.

Read about our teams working on gene therapies →

X-Chromosome reactivation (females only) diagram

Base editing

This technique corrects tiny spelling mistakes in the DNA. 👉 Like fixing a single typo in a long document. Very precise; no extra DNA is added (reducing risk). Delivery to the brain remains challenging and it is still experimental.

Will it work for CASK disorders?

Works best for correcting single-letter DNA changes (point mutations) rather than larger deletions, insertions, or complex rearrangements — making it not applicable to many in our community.

Base editing diagram

Prime editing

A more advanced version of gene editing that can fix a wider range of DNA errors. 👉 Like using "find and replace" to fix whole sections of text. Very flexible and can correct more complex mutations, but still at an early stage of development and appears complex to deliver.

Will it work for CASK disorders?

Theoretically it could work for all types of CASK mutations. However it is still being developed and needs a lot of work before it can reach clinical trials in humans.

Prime editing diagram

RNA editing

Instead of changing the DNA, this fixes the message it sends to make the protein. 👉 Like correcting a photocopy of instructions that will be used to make the product, rather than the original document stuck inside the library. Potentially much safer than tinkering with DNA, but the effect is temporary so treatment may need repeating.

Will it work for CASK disorders?

Would only work for some specific mutations and comes with delivery challenges (getting it into the right cells). Very early in development.

RNA editing diagram

RNA trans-splicing

Replaces faulty parts of the gene's message (the RNA) with healthy sections. 👉 Like cutting out a damaged paragraph and inserting a correct version. Like RNA editing it avoids permanent gene changes but comes with the same disadvantages. Still in very early stages.

Will it work for CASK disorders?

A clever approach, but difficult for CASK disorders. CASK mutations are spread across the gene, so multiple therapies would have to be created. Works best for inherited disorders where many patients have the same mutation (e.g. sickle cell anaemia).

RNA trans-splicing diagram

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