HSP research update September 2015

Progress report from the research team


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

Principal Investigator, Prof. Alan Mackay-Sim provided this report:


Science is never predictable and the last 3 months in the lab have been slower than hoped, for both technical and biological reasons.

The technical problems have been with the half-million dollar microscope system used for imaging living cells. The problem has taken a while to diagnose due to the complexity of the instrument but it is now repaired and working properly, however time has been lost. Other technical issues arose with the purchase of new reagents that do not behave as the old ones did. This has taken some trouble shooting and re-optimisation by Fan.


Fan in animal breeding lab
Dr. Fan in animal breeding lab

The SPAST (SPG4) mutated mice are now through all the regulatory, supply and quarantine hurdles and are now being housed in facilities at Griffith University, having previously been housed at the University of Queensland for quarantine.

Mice with SPG4 HSP
Mice with SPG4 HSP

Our thanks to Dr Andy Grierson and his team at the University of Sheffield who supplied the breeding pairs and to Emily Duggan at the University of Queensland who arranged their importation and quarantine for us.

Initially one mouse quickly became pregnant but the first litter was lost early on, possibly due to the stresses of travel on the parents. Since then all have behaved well with the first successful litter now a month-old with others following. Fan is genotyping them to identify the next generation of mutated SPAST mice.

Prof. Mackay-Sim, Dr. Fan & HSPRF Pres. Frank McKeown
Prof. Mackay-Sim, Dr. Fan & Pres. Frank McKeown


A paper based on Gautam’s research work was submitted to a journal for review and, although rejected, received some useful feedback from the referees. We are taking their advice and will do another couple of experiments that will help pin down how peroxisome transport deficits in SPAST cells can lead to cell death.

Gautam’s work on establishing induced pluripotent stem cells to differentiate into neurons with the SPAST mutation is continuing. Earlier this year, Gautam generated induced pluripotent stem cells (iPSCs) from an HSPer with a SPAST mutation and from two healthy people as controls.

iPSC process
iPSC process
Gautam Wali
Gautam Wali

Over the last few months he has been testing batches of iPSCs to make sure that the required genetic engineering was successful. These quality control experiments are essential for reliable science and include measures such as chromosome stability, differentiation potential and pluripotency status. Uniform populations of iPSCs are notoriously hard to establish due to the variability across the cell population following the genetic engineering. For any results from subsequent downstream testing to be reliable, the cell population being tested must reach a high standard of uniformity in order to make meaningful comparisons of the data produced.

Gautam is now working on differentiating the iPSCs into neurons. This involves growing them for several months in a complex mix of proteins, growth factors, ions and sugars. These cell colonies are fragile; they must be fed with fresh growth medium every few days and demand closely controlled environmental conditions. The purpose is to mimic the growth conditions in the developing human embryo, aiming to turn the iPSCs into cortical neurons, which is the type of nerve cell most affected in people with HSP. The procedure is long and complicated, fraught with difficulty and randomness, still part “art” as much as “science”. When all this comes together he will have human neurons that will be used to further test his earlier findings of the effects of SPAST mutations on peroxisome trafficking and the efficacy of drug treatment candidate, epothilone D.


  1. my wife has had spg7 for 18yrs which obviously has gotten worse the last 6yrs she has been confined to a wheel chair we have tried everything from acupuncture to spiritual healing. if this drug would ease the pain and suffering and is safe we would definetly be interested. also if u have any advice or medication that we haven’t tried we would luv to hear it 🙁

  2. I am resident in UK and have a ex wife and step daughter who have both have HSP. They both started having HSP around the 40 years mark. The ex wife is 73 years and the step daughter is 51 years and the wife has been wheelchair bound for about 15 years but can rise for showers and toilet but with great difficulty and just determination. The step daughter can just but walk but I feel this is due to her heroic behaviour on her part, she has never married and is childless, but I think 2016 will be her last year walking unless of course you may come up with a cure. I also have two daughters by the ex wife one is 43 and childless and the other is 40 who has 3 children and neither is showing any HSP signs or the grandchildren 2 boys 12 and 14 1 girl of 16 years no sign of HSP. I have been donating since I came across the australian website searching for news about HSP and they have told me the HSP search cure is worldwide not just australia so I hope my family will 😛 😛 get any benefit particularly the step daughter who has been a real star and I hope the cure is not too late to help her life be easier and enjoyable. So very good luck and speed for you to find a cure. I am in daily contact with my ex wife and step daughter and the rest of my family although I dont live near them and I do link up with them occasionally. The ex wife and step daughter are very keen to help with any trials you are doing but my daughter with the 3 children knows nothing about this and will not from me to stop her worrying her needless. best wishes in your
    search. Any more information you need please contact me. Good luck again. KEITH

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