Growing human brain tissues to study rare disease

01 December 2017
Dr Nayler and team create cerebellar neurons (source: Drew Hayes)
Dr Sam Nayler, an Early Career Research from StemCARE at the University of Queensland, recently completed a study which focussed on using a human model system to investigate the role of genetic mutations in a rare neurodegenerative disease. The first author on the paper in Frontiers in Cellular Neuroscience, Dr Nayler and the team have taken an important first step towards understanding the disease and screening chemical compounds for treatment. 

Ataxia-telangiectasia (A-T), also known as Louis-Bar syndrome, is a debilitating disease caused by mutations in the ataxia-telangiectasia (ATM) gene – a gene involved in repairing damage to DNA. Studying this disease is incredibly difficult, as animal models cannot clearly mimic the neurological aspects of this disease.

Another approach is to create model tissues from stem cells taken from patient samples. The Wolvetang Group, of which Dr Nayler was a member, took samples of skin from patients and reprogramed them to become induced pluripotent stem cells (iPSCs), which have the potential to grow into virtually any cell type, given the right circumstances. In this case the technology was used to produce cerebellar neurons to better understand the mechanisms underlying the disorder. 

“By propagating iPSCs, the goal is to develop a human model system that can be used to examine the consequence of ATM mutation in a controlled laboratory environment in a cell type relevant to the disease with the aim of identifying drugs that can help these children,” commented Professor Wolvetang, the lead researcher. 

“It’s a terribly debilitating disease with fatal consequences. The first signs of A-T appear during early childhood, and most suffers are wheelchair-bound by their teens. The symptoms become progressively worse with time,” Dr Nayler said. The use of patient-specific iPSC offers great opportunities to gain insight into the genetic basis of this neurological disease.

“The end goal is to produce a model of the disease with which we can use to screen shortlists of potential therapeutic agents, which could halt the disease and improve the quality of life of these people. But first we really need to understand it,” Prof Wolvetang concurred.

Dr Sam Nayler was awarded the prestigious two-year Oxford Nuffield Medical Fellowship to study the mechanisms underlying A-T and is currently continuing this research at Oxford University. After his time at Oxford University, Dr Nayler will return to Australia and bring with him new insights and novel techniques.

“Currently, no researchers in Australia, except for the Wolvetang laboratory, are working on human iPSC-derived cerebellar neurons, so my aim is to return home from Oxford and make a significant mark in this space,” he said.

A-T research in AIBN’s Wolvetang Group is a collaborative effort with Professor Martin Lavin’s laboratory at the UQ Centre for Clinical Research and is supported by the BrAshA-T charitable foundation. Other collaborators include Dr Joseph Powell at the UQ Institute for Molecular Bioscience, and Professor Christine Wells at Melbourne University. 

The Oxford Nuffield Medical Fellowship is funded by the Nuffield Dominions Trust, and administered by the Australian Academy of Science.

Professor Ernst Wolvetang and Professor Christine Wells (Deputy Program Leader) are Chief Investigators with Stem Cells Australia.  

For more information:
Read the journal article.