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First Australian Research Initiative

Development of CASK Patient Derived Pluripotent Stem Cells (iPSCs) and Drug Screening for potential treatments to mitigate the effects of CASK

Background

Professor Ernst Wolvetang, Dr Selin Pars, and Professor Stefan Thor at The University of Queensland (“UQ”) are leading an advanced research program using CASK patient-derived induced pluripotent stem cells (iPSCs). By studying these iPSCs and their behaviour, the team aims to uncover the underlying mechanisms of CASK and how different mutations manifest in individual children. A major objective is to screen a wide range of therapeutic compounds to identify those that may help reduce the effects of the disorder.

This personalised approach uses cutting-edge stem cell and organoid technologies to create human “mini-brains” in a dish—brain organoids that carry the same genetic makeup as a patient’s own brain. These organoids allow researchers to safely and precisely test potential treatments without placing the patient at risk.

Research into CASK is ongoing in laboratories around the world, with many studies using animal models because the CASK gene is present across most species. While these models have provided important insights, they cannot fully replicate human biology. For this reason, research using human-derived cells is of enormous importance.

A key method enabling this work is cell reprogramming. Blood is collected from patients and healthy controls (often the patient’s biological parents), and these blood cells are reprogrammed into stem cells that resemble early embryonic cells. These stem cells can be grown in large numbers, frozen, stored, and shared with research groups internationally.

Human reprogrammed stem cells can then differentiate into most—if not all—cell types found in the human body. They can also self-organise into organ-like structures known as organoids, engineered to resemble specific organs such as regions of the brain, the liver, or the heart.

Because different CASK mutations can result in varied clinical outcomes, generating stem cells from multiple patients allows researchers to study these differences in detail and may ultimately open pathways to personalised treatments.

 

What are the Goals of this Research Project?

The short-term goal is to understand the problems with CASK mutant stem cells as they are differentiated into a number of different cell types and organoids, with the initial focus being on brain organoids.

The long-term goal is to develop treatments for CASK individuals.

CASK_hiPSC_schematic

Building the Future of CASK Research in Australia

The publication of the first Australian-led research article on CASK-related disorders marks an important milestone for Cure CASK, Australian families and the wider global CASK community.

This first study reflects the beginning of a dedicated Australian research effort led by researchers at The University of Queensland, using patient-derived stem cells to better understand CASK-related disorders and how they affect brain development and function.

You can read the first published study from this project here:
Read the first CASK study

The University of Queensland research team is now preparing an application to the Medical Research Future Fund (MRFF) together with Cure CASK, with the goal of expanding Australia’s contribution to global CASK research. For this application to be as strong as possible, it is important to demonstrate meaningful community engagement and interest from families affected by CASK.

We encourage Australian and international families affected by CASK-associated conditions to express their interest in participating in this research. At this stage, there is no obligation or commitment. The purpose is to help show the need for this work, strengthen future funding applications, and ensure families can be kept informed as the research develops.

Future participation may involve providing a blood sample, sharing clinical information, or contributing lived experience insights. Any future participation would be subject to appropriate research approvals, informed consent and further information from the research team.

The development of CASK patient-derived stem cell lines is more than one research project. It creates a foundation for future studies, collaborations, drug screening programs and therapeutic development. These critical research resources may help scientists better understand the biological mechanisms of CASK, why symptoms vary between individuals, and which pathways may be targeted by future treatments. This research is focused not only on understanding CASK, but on accelerating the pathway toward interventions that may improve the quality of life of those living with CASK-associated conditions.

Importantly, this work is already part of a wider international research effort. Cure CASK is helping support collaboration between the Australian UQ team, our research partners at UC Davis involved in the CASK reactivation project, Katsuhiko Tabuchi, M.D., Ph.D. in Japan, and our international CASK Coalition partners.

Together, we have an opportunity to ensure families play a leading role in shaping the future of CASK research in Australia and globally.

Expression of Interest:
Families who would like to be kept informed or may be interested in participating in future CASK research are encouraged to contact Cure CASK at giovi@curecask.com.

Please see Professor Ernst Wolvetang video which was launched at the ACNRF Annual Gala where he explains the process of creating brain models from blood cells and highlights the use in studying neurodevelopmental and neurodegenerative diseases 

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Lavvina Thiyagarajan

MBBS

Lavvina is a clinical genetics fellow from NSW, Australia with a background in general paediatrics. She has practiced in multiple tertiary paediatric hospitals in Australia, both in general paediatrics and clinical genetics. She currently provides specialist advice for the NGO, Taking Paediatrics Abroad and is a member of GeneEQUAL, an inclusive research group aiming to improve accessibility of genetic testing and care for people with intellectual disability by co-design.

Lavvina’s clinical interests are in the genetics of autism, intellectual disability and immunogenomics. She is particularly passionate about including the patient groups she works with in research and healthcare decisions.

Lavvina is affiliated with The Children’s Hospital Westmead and the University of New South Wales where she is undertaking a Masters by Research, co-producing a model of genetic healthcare that aligns with the preferences of Autistic people.

Permission to Use Photos and Media

I, the undersigned, give my consent to the Angelina CASK Neurological Research Foundation Ltd and Angelina CASK Neurological Research Foundation Inc (ACNRF) to use photographs, videos, or other media featuring me, my child, or an individual under my legal guardianship (“Media Materials”).

This consent permits ACNRF to use these Media Materials for purposes such as:

  • Raising awareness of CASK-related disorders
  • Promoting ACNRF’s initiatives, campaigns, and programs
  • Sharing on ACNRF’s website, social media, newsletters, and other communication channels
  • Use in advertising, educational resources, and fundraising efforts.

I understand that these materials may be distributed publicly and may appear in print, digital, and other media formats worldwide and in perpetuity.

Terms and Conditions:

1. Usage Rights: I grant ACNRF the right to edit, adapt, or modify the Media Materials as needed for the purposes outlined above.

2. No Compensation: I acknowledge that no monetary or other compensation will be provided for the use of the Media Materials.

3. Release of Claims: I waive any rights to inspect or approve the final product and release ACNRF from any claims, liabilities, or damages related to the use of the Media Materials, including but not limited to claims of defamation, privacy, or copyright infringement.

4. Ownership Confirmation: I confirm that I have the authority to grant these rights for the provided Media Materials and that they do not infringe on the rights of any third party.

This authorisation is voluntary and may be revoked by written notice to ACNRF at any time, though I understand that materials already published may not be withdrawn.

“In some ways, that CASK-linked pathology is degenerative in nature provides a positive outlook. Because microcephaly in CASK-linked pathology progresses postnatally, there may be a temporal window when therapeutic intervention might prevent or slow further brain cell loss. Regression, even in adolescence, has also been observed in some cases of MICPCH [119], again offering the tantalizing possibility that a therapeutic approach might prevent such decline under conditions when degeneration is known to progress. The potential benefits of intervention might extend even further given that non-cell-autonomous toxicity could also affect functioning of the remaining neurons; reduction of such toxicity, especially when coupled with high-intensity rehabilitative measures [120], might offer real hope for a positive impact on functional outcomes.”   

https://www.mdpi.com/2073-4409/11/7/1131/htm