Research Update June 2016

Progress report from the research team 


Editor’s Note: New publication in scientific journal announced 27 May 2016

The research team have been successful in having important work accepted for publication in the nature publishing group journal Scientific Reports. Acceptance for publication is through a peer review process, which, in the world of science, is the stamp of approval of valid findings based on sound science. The paper represents a major stake in the ground in the HSP research program that is supported by this Foundation and the SP Foundation in the USA.

The paper explains the mechanism of how the lack of certain proteins in SPAST (SPG4) HSP nasal stem cells affects the microtubules in the cells, causing organelle trafficking deficits, leading to stress in the cell and significant functional impairment. The paper also details the rescue and restoration of impaired function achieved with a drug that has the potential to be an effective treatment for this form of HSP.



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

Prof Mackay-Sim reports on research work over the last 3 months:

Both drug validation studies, that is, testing the effect of drugs on HSP mouse neurons in one and on human HSP neurons in the other study, have seen positive progress over the past 3 months. However there have been both technical and equipment issues that are causing delays in both studies.

Whilst some drug testing has now been performed on the human HSP neurons, analysis of the data is yet to be done and so results are not yet available. Drug testing has yet to be done in the mouse study. Therefore, it is not yet known if the effectiveness that was previously found with the drugs on human HSP nasal stem cells also applies to the HSP mouse neurons or to the human HSP neurons.

A key measure in both studies is the trafficking of peroxisomes – how that is affected in both mouse and human HSP neurons, how it compares with non-affected cells, and how the drugs being tested impact this trafficking. In the earlier research work using human HSP nasal stem cells, a fluorescent label or marker that attaches to every peroxisome was created and developed as a sensitive and effective measure of their position, movement and speed over time using imaging technology that picked up the fluorescent marker.

However in both the human and mouse neurons in the current studies, the fluorescent marker successfully labels only a very small percentage of the peroxisomes. This labelling technique is now being optimised for these neurons. It is vital to again discover an effective way to measure peroxisome trafficking in these different type of cells and concerted efforts are currently being directed to that end.


Dr. Yongjun Fan
Dr. Yongjun Fan – Mouse Study
Dr. Gautam Wali - iPSC Study
Dr. Gautam Wali – iPSC Study

HSP Mouse study

Here is some more detail on the HSP mouse drug validation study. Since the last report, the mouse breeding program has continued to reliably provide new mouse pups each week. A delay currently standing at 6 weeks has been caused by malfunction of the computer controlling the imaging microscope. New parts and repairs are expected to be completed soon. This study, while also subject to peroxisome trafficking measurement difficulties, has not been affected to the same extent as the iPSC study and sufficient markers have allowed for calibration imaging to go ahead. Overall, this study is estimated to be 2 months behind schedule.

iPSC study

Here is some more detail on the human HSP neuron drug validation study using induced pluripotent stem cells (iPSC). Since the last report, reprogramming and differentiation of cell lines with new batches is continuing, resulting in a total of 19 cell lines from 3 SPAST HSPers , 2 SPG7 HSPers and 3 non-affected controls. Drug testing and data collection have begun, however analysis and the production of results is on hold while an effective form of peroxisome labelling and measurement is established in these particular types of cells. Currently this study is also estimated to be 2 months behind schedule.




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