Stem cell research update September 2014

Progress report from the researchers


Highlights include:

  • a 3rd potential drug candidate being investigated

  • new findings about trafficking defects in HSP cell organelles

  • work starts on the induced pluripotent stem cell project in Sydney in early September.

Dr. Yongjun Fan
Dr. Yongjun Fan

Dr. Yongjun Fan

Over the past 6 months I have been investigating a third potential drug candidate for treating HSP using assays that measure the expression of acetylated alpha tubulin and peroxisome trafficking in HSP stem cells. By looking at the level of acetylated alpha tubulin in these cells after treatment with a serial dose of this drug, we identified the dose which can recover acetylated tubulin to an exactly normal level in HSP cells without affecting cell metabolism and cell proliferation.  The effect of this drug at this dose on the peroxisome trafficking is under investigation. The effects of this drug as well as the tubulin-binding drugs on differentiated neuron-like cells will be investigated in the next few months.



Prof. Alan Mackay-Sim
Prof. Alan Mackay-Sim

Prof. Alan Mackay-Sim


HSP mouse project

The mouse project is ready to go … all we need are the mice! We have the ethics approvals and have made the requests to import the HSP mice from England. The importation is being held up by red tape, waiting for approval to export from the UK and approval to import into Australia. it is a very normal practice to send mouse strains around the world for researchers to share, so hopefully we will not have to wait much longer for their arrival.

Induced pluripotent stem cell (iPS) project

This project is taking place at the Kolling Institute at Royal North Shore Hospital in Sydney under the guidance of Prof Carolyn Sue. Griffith University-based researcher Gautam Wali is moving to Sydney in early September to undertake the project, starting with establishing a bank of induced pluripotent HSP stem cells.

Both the mouse project and the iPS project are designed to further test the validity of the successful effects on HSP stem cells of the 2 candidate drugs already identified. This step is necessary in making a good case to the Therapeutic Goods Administration for approval for human clinical trials.

Simon Weyers has now completed his time with the stem cell team after presenting his research at two overseas conferences during May. He has now returned to Germany with our thanks for his efforts and our best wishes for his future.


Gautam Wali
Gautam Wali

Gautam Wali

We have now successfully differentiated neuron-like cells from HSP stem cells. The axonal processes of these cells are like the axons of cortical neurons (the nerve cells in the brain stem that are degenerated in HSP). They have no actin cytoskeleton and hence peroxisome trafficking depends entirely on the microtubule cytoskeleton.

We have been delving deeper into peroxisome trafficking along these axonal processes. We found that there were fewer peroxisomes in the axonal processes of the HSP cells compared to normal cells. The HSP cell processes also had significantly fewer microtubule dependent fast moving peroxisomes. Additionally, there was an imbalance in the retrograde (heading back towards the cell body) versus anterograde (heading away from the cell body) peroxisome transport in the axonal processes of the HSP cells. There was no difference found between HSP and normal cells in the time-dependent dynamics that characterised the movement of microtubule dependent fast moving peroxisomes in the axonal processes.

These experiments demonstrate that the neuron-like HSP cells exhibit amplified peroxisome trafficking defects compared to previous studies in standard HSP stem cells, that is, these defects are worse in the long arm of these neuron-like cells. These findings provide a platform to further study peroxisome trafficking characteristics such as retrograde/anterograde peroxisome movement.

We expect that similar and even more severe deficits in peroxisome trafficking occur in the cortical neurons of the brainstem of people with HSP, as for these neuron-like cells.





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