In the brain of every female with a CASK gene mutation, there are silenced copies of the healthy CASK gene. The project is proposing to “turn on” these silenced genes. The genes will then be able to create the CASK protein.
This will, theoretically, result in a brain which, initially having just half of the CASK protein needed to function properly, will have much more. This should have a dramatic impact on the prognosis of the disease since the brain will now have enough of the CASK protein needed to function properly.
This project involves 2 Phases:
- Creating human induced pluripotent stem cells, growing them in a dish and turning them into different types of brain cells in order to evaluate the efficacy and efficiency of the approach. This First Phase is now fully funded and will be commencing on 1 February 2024 and subject to the progression of this Phase we anticipate completion about 31 July 2025.
- Characterizing mouse models of Cask. This will include assessing the ability of the therapeutic to reactivate the healthy copy of Cask in the brain of mice and test the level of recovery this approach could have.
CASK aims to follow in the footsteps of two more common Xlinked genetic disorders: MECP2 and Rett syndrome. Xreactivation has successfully been done (in mice models) for the two genes that cause these neurological disorders. UC Davis is eager to have the opportunity to try their technique on the CASK gene – a gene that displays all the markers of being a successful candidate for this novel therapeutic.
The UC Davis MIND Institute located in California is a collaborative international research center, committed to the awareness, understanding, prevention, and treatment of the challenges associated with neurodevelopmental disabilities and rare x linked disorders.