Promising progress… and a long way to go
Prof Alan Mackay-Sim, co-Principal Investigator of the HSP research program, gave a progress report on the research projects underway.
He highlighted the difficulty of further accelerating the research with current funding and resources available.
The majority of funding comes from a National Health and Medical Research Council grant of just over half a million dollars over 3 years that is now in its last year. Combined with the support from this Foundation, it has been possible to increase the number of researchers dedicated to finding a cure for HSP from not quite one full-time equivalent to the current level of around 4 full-time equivalent researchers.
This has had an enormous impact on the scope of research possible and the progress made to the point we are today of examining 2 potential drugs that are promising candidates for a clinical trial. However, realistically, what it will take to satisfy the Therapeutic Goods Administration (TGA), Australia’s regulatory agency for medical drugs and devices, to approve a clinical trial is still some way off. Here is a report on the work currently underway with that goal in mind:
Gautam Wali is partnering with Dr. Ratneswary Sutharsan, who manages the stem cell bank and also has special expertise in statistics, in analysing data on peroxisome movement on microtubules in HSP stem cells. They are studying multiple characteristics of the movement of peroxisomes in great depth with the aim of specifying the particular part of the mechanism and process that is affected in HSP cells. This is necessary as part of the requirement to know exactly how the drug candidates are acting on the impaired peroxisome function.
Simon Weyers is introducing DNA into HSP stem cells, aimed at getting them to make the spastin protein that they are lacking and observe the effects on other proteins in the causal chain. This study is seeking to confirm that the SPG4 gene mutation is indeed causing the effects and impairments observed in the cells. By elevating spastin levels, it is hypothesised that this will lead back to normal microtubule formation and peroxisome movement. He will then do the opposite in unaffected stem cells, attempting to induce the impairments expected from HSP by artificially decreasing spastin levels, which is predicted to cause HSP-like changes in cell functions. This has the potential to unambiguously confirm how the genetic mutation is responsible for the bundle of effects and impairments observed in the stem cells that are characteristic of HSP.
Undergraduate Honours student, Johanna Fernandes, is continuing her investigation into lysosome function/impairment with HSP, which has now grown into a separate project in its own right.
Developing Neuron-like Cells
Dr. Yongjun Fan is continuing his work on differentiating neuron-like HSP cells from nasal HSP stem cells. This is proving to be both slow and difficult, but necessary in order to test the findings of other research work to date to see if the same results can be achieved in the long arm (axon) of neurons (nerve cells) as have been found in stem cells. Drugs to cure HSP will need to reach and function effectively in the upper motor neurons in the brain.
HSP mouse project
This project has now been initiated with application for ethics approval. Also the importation process for HSP mice breeding pairs in collaboration with the University of Sheffield in England is underway. More details on this project will be provided as the planning unfolds.
Planning & Project Funding
Foundation President, Frank McKeown, met with Prof Mackay-Sim at the National Centre for Adult Stem Cell Research on the Brisbane campus of Griffith University in mid-February to discuss plans for HSP research in the Towards a Cure program in 2014 and beyond.
Frank commented “Continuing success in testing the promising drug candidates under review could result in an application to conduct clinical trials on HSPers as early as sometime in 2015. It’s hard to imagine that we have come so far, so quickly, with relatively so few resources… and now we are thinking ahead to testing potential drug cures on HSPers. That’s the good news. What isn’t so good is that we had a significant shortfall in our 2013 fundraising target and I fear that if the reduced fund raising trend continues in 2014, it will at the very least slow the pace of research, and even possibly lead to important projects being shelved for now… pushing the whole time frame out significantly. That would be a real shame for people everywhere who are waiting for a cure that they desperately want and need.”