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 gene replacement work for CASK disorders?
Gene replacement has been successfully licensed for some genetic diseases, including neurological disorders such as spinal muscular atrophy (SMA) and AADC deficiency. However, gene replacement is not necessarily a universal solution for every type of CASK mutation.
For children with CASK variants that result in little or no functional CASK protein, replacing the missing function may be a logical therapeutic strategy. But some CASK mutations — particularly missense mutations — leave the cells producing CASK protein that may be partially functional or altered in its behaviour. Different mutations can affect different regions and functions of the CASK protein.
Will simply adding another copy of CASK correct the underlying problem for every mutation? We don't yet know.
Similarly, CASK copy-number changes, mosaic variants and other mutations may have different biological mechanisms. A treatment that increases CASK production may not necessarily be appropriate where the underlying problem involves an altered protein or abnormal gene dosage.
For gene replacement to be successful, we also need to establish the appropriate level of CASK expression, safely deliver the therapy to the relevant cells throughout the brain, and understand the risks associated with the delivery method and immune response.
There are also important safety considerations for any experimental gene therapy.
This does not mean that gene replacement will not work for CASK — it may ultimately be an important treatment for some children. But we cannot assume that one approach will work equally well for every CASK mutation.
