Contact person: Associate Professor Tony Cook
Using induced pluripotent stem cells to model childhood dementia
An estimated 2 million Australians – 8% of the population - live with one of >7,000 rare diseases . Of note, there are >70 rare genetic diseases that cause childhood dementia and pre-mature death, and which affect >2,000 Australians and their families . Batten disease (also known as neuronal ceroid lipofuscinosis) is one such disease, and which affects ~1 in 100,000 children born in Australia. The progressive and disruptive effect of Batten disease on the brain impacts the person’s ability to carry out tasks associated with daily living, resulting in high care needs, with premature death occurring on average at 14 years of age . Despite the identification of >12 genes that cause Batten disease, the mechanisms contributing to neurodegeneration are poorly understood. Our research focuses on Batten disease caused by CLN3 gene variants, which account for ~30% of the disease burden.
To investigate how variants in CLN3 affect the cells of the brain, we have used advanced techniques in stem cell biology and gene editing technology. The major advantage of this technology is that it utilises a person’s own cells (e.g. skin fibroblasts), complete with inherent causative variants, to generate stem cells in the laboratory, that can then be matured into brain cell types for research. When coupled with gene editing techniques, it is possible to conduct experiments using cells where the only genetic difference is the disease-causing variant in the CLN3 gene. This approach enables us to answer highly specific questions about how CLN3 causes Batten disease, and thereby will (i) provide targets that will facilitate drug repurposing or drug screens to identify novel lead molecules, and (ii) provide a means to rationally select, test and determine the efficacy of novel combinatorial therapeutic strategies targeting CLN3 variants.
 Rare Voices Australia & Department of Health. (2020).
 Childhood Dementia Initiative. https://www.childhooddementia.org/whitepaper, (2020).
 Tilden. https://www.childhooddementia.org/burdenstudy, (2020).
To further understanding of how brain cell types are affected by genes that cause Batten disease, and thereby generate mechanism-driven hypotheses regarding new treatments.
- Dr Sharn Perry
- Prof Anna King
- Prof Alex Hewitt
- Batten Disease Support and Research Association Australia
- Royal Hobart Hospital Research Foundation
Other support into neurodegeneration:
NHMRC, FightMND, MNDRA, ARC
To hear more about A/Prof Cook’s team and their research, you can view a recorded public seminar from April 2021: