Stem cell research report

What has been achieved and where to from here


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

A report to the HSP community by Prof. Alan Mackay-Sim, Director of the National Centre for Adult Stem Cell Research and Co-Principal Investigator of the HSP research study program.


It was a satisfying achievement to finally publish the results of the last 3 years work that was supported by funding from the HSP Research Foundation. It is now available in a journal that is accessible to everyone and is featured in this edition of Research Highlights on this website.


The study concentrated on understanding how cells from HSPers and non-HSPers differed, in order to learn how the genetic mutations in the spastin gene lead to the disease. We found some key differences in HSPers’ cells that suggest how the nerves in the spinal cord are affected. These differences concern the microtubules, part of the internal skeleton of every cell, that are involved in transporting “energy cargoes” around cells and especially along nerves. Microtubules are normally being formed and reformed constantly in cells.


Knowing what we know about spastin, we expected that spastin mutations (lower levels of spastin) would lead to more stable microtubules (not a good thing), but found an unexpected drop in the levels of stable microtubules. On closer inspection we found that another protein, stathmin, was in higher levels than expected, effectively compensating for the reduced spastin, and the reason for the level of microtubule stability measured. Why is this important? Mainly because it gives us a better idea of how the disease affects cells and what cell processes to investigate when screening for potential drugs. So we studied the effects of two drugs whose effects on microtubules are well known. This research showed that very, very low doses of the drugs could restore the microtubules in HSP cells to normal.


Dr. Yongjun Fan
Dr. Yongjun Fan

What are we doing now? Fan is now experimenting on several potential drugs of the same family, which have greater ability getting into the brain and spinal cord, as this is where they will need to finish up to be effective in treating HSP. Some drugs in this family are not able to get into the brain and spinal cord, and all are toxic to healthy cells at the concentrations in which they are used to treat cancer, so the challenge now is to identify ones that:

          • restore HSP cell functions to normal
          • can successfully get into the brain and spinal cord to do their work
          • are effective in very low concentrations, and
          • are safe to use on an ongoing basis.


The next stage of drug discovery is to validate candidate drugs by testing them on different cell functions, especially on cell functions associated with the disease. The team is following a number of paths here.


Fan is working on methods to turn the olfactory stem cells into nerve cells (neurons) because these will have long axons, like those that make up the nerve tracts of the spinal cord that are affected in HSP.


Gautam Wali Ph.D. candidate
Gautam Wali Ph.D. candidate

Gautam and Simon are studying how the spastin mutations affect the dynamics of cargo transport inside HSP stem cells and “neuron-like” cells with long axon-like processes.


Gautam has been using time-lapse videos to follow how far and how fast the ‘cargos’ travel inside cells. Already we know that one type of cargo travels slower. Why are we doing this? The goal is to find disease-associated differences in cell functions related to what happens inside the long axons in the spinal cord nerves of HSPers. Levels of these altered cell functions are then used as part of the screening process to find drug candidates that may be effective.


Simon has developed ways to see the microtubules being formed inside the cells. Time-lapse videos show the new microtubules as little comets. He is seeing if HSP and healthy cells have different numbers of newly forming microtubules and whether their speeds of formation differ.


Where are we going in the next year?


Fan will be:

  • completing the work to make HSP neurons
  • completing the analysis of the tubulin-binding drugs, and
  • starting on the screening of our library of 800 drugs already in use for other diseases.


Gautam will be:

  • completing his analyses of cargo transport in HSP stem cells and neuron-like HSP cells
  • assaying the neurons made by Fan
  • assisting Fan in the drug screening work.


Simon Weyers
Simon Weyers

Simon will be comparing and contrasting stem cells with and without the spastin mutation. This will be important in learning if drugs for people with mutations in spastin might be effective for those with other HSP mutations.


Gautam and Simon will together be doing some deeper biological analyses aimed at finding out more about exactly how the spastin genetic mutations cause the effects that have been observed in HSP stem cells. This is important for understanding how drugs that are effective might be working.


The next stages of research will be to test any candidate drugs in mice with spastin mutations. We are planning for this eventuality and negotiating to collaborate with international researchers who have genetically engineered mice suitable for this purpose. We are also in discussion with Dr. Carolyn Sue, who has collaborated on the stem cell research to this point, to work together on “induced pluripotent stem cells” from HSPers. These are skin cells that have been genetically engineered to turn them into stem cells. This type of stem cell is all the rage at the moment and they can be turned into many types of neurons, including neurons like those in the affected part of the HSP brain. These will also be used to validate any potential drug candidates that we discover and to test for their toxicity on brain cells.


  1. Thank You for your research and caring about those affected with HSP. I have watched my husband suffer with HSP for years and have prayed for a cure. You are making that possible with your research I cannot thank you enough for restoring my hope!



  2. Thank you so much for your hard work. As the mother of a child with a severe form of HSP, I can’t even begin to describe to you how exciting it is to read something (written in plain English) that sounds like a real treatment might someday come out of it!

    Good luck!

  3. Thank you for this very important research. I have been living with HSP since age I was 10
    years old and welcome any progress for treatment.

  4. Hi.
    I am interested in why you think this will work. If you repair the spinal cord via stem cells, but the condition is known to progress through the long nerves in the body (ie lower limbs) – and you don’t fix these problem nerves, then how will the condition be mitigated?

  5. Ed. Note:
    Hi Aaron, there is no intention to repair the spinal cord via stem cells. Stem cells are being used as a way to study HSP. The aim has always been to find a drug cure that would reverse or compensate for the significant impaired cell functions caused by an HSP mutation.

    Secondly, while the impaired nerve signalling affects the lower limbs, the origin of these problems is the long nerves (neurons) in the brain stem. HSP is what is known as an upper motor neuron disease.

  6. Research for this disease seems to be very slow. But maybe each discovery will someday complete the puzzle. Thank you for the research.

  7. Is there any hope that this research will lead to a treatment for primary lateral sclerosis too? I have been diagnosed with the condition (12 years ago). When the research begins trials with people, I’m sure you will find lots of us willing to participate! Thank you! Thank you! Thank you!

  8. Ed. Note:
    It is quite possible that a treatment breakthrough on any of the “cousins” within the family of similar neurodegenerative diseases such as PLS, HSP, ALS, CMT etc could lead to a treatment for one or more of the others. Researchers in this area tend not to be disease-specific, often studying several diseases that have significant similarities. It is not uncommon for findings and discoveries on one disease to help increase the knowledge and understanding of others.

    The stem cell research reported on here is focused on SPG4 HSP, but the researchers are finding similar patterns of significant impairment in other autosomal dominant HSP mutations, so raising the possibility that a cure for one might also be a cure for others.

    There is good reason to be confident that any treatment breakthroughs will be leveraged to the fullest extent for their ability to deal with other conditions, if for no other reason than it saves huge amounts of time, effort and money to test proven cures for one condition on others, and this process is well-established in research.

  9. Grateful for the research being done for HSP! I hope that it comes with a cure in my life time! I would like nothing more than to pay hockey once again, hit the slopes skiing, playing a round of golf, and hey… Just to go for a run…. Ahhh dreams!

  10. My brother and I are both diagnosed as having HSP which came on in our early forties, but the biggest worry we both have is for our children. To know you are doing research with stem cells gives us some hope for them even if it’s not going to happen for us. We would love to just be able to take a walk comfortably but the guilt of passing this condition on makes me feel guilty everyday and is the hardest thing to live with. We look forward to hearing some positive results from your research. Many thanks to you all

  11. I was told a few years back by my sister that Professor Nicholson @ Concord Hospital mentioned I possibly had the condition despite the fact I was a very sporting person who surfed, played touch football, and did a lot of running. After a diagnosis of my great niece recently identifying the gene affecting her, I decided to go for blood tests recently to confirm if I have it. I have an athritic knee which affects my walking, so unsure if its that problem or a combination. With the research being done so that future generations may have some type of treatment, it is fantastic as many of my family members suffer to different degrees of the condition, some worse than others. Find that cure please.

  12. Great work! I am very grateful and looking forward to any results! I have been affected for 7 years and can hardly walk now! In Europe there is not much information about your research* Found it by chance* Wish you all the best for good and effective results* let me know if there is any testing phase – I would like to take part* Best Claus (France)
    😎 😎

  13. My mother passed away four years ago yesterday, February 17th. She had Primary Lateral Sclerosis (PLS) that progressed into Lou Gehrig’s Disease (ALS).
    I am so grateful to hear of ongoing research and I continue to pray for a cure. God bless y’all!

  14. I’ve had HSP my entire life and it has started to progress significantly now that I’m in my mid-30’s. Is there any indication of a timeline as to when some medications/cures may be available? Are we talking something like 5 years or 50 years? Thanks!

    1. Editor’s note: Prof Alan Mackay-Sim, Principal Investigator on the Towards a Cure for HSP research program addressed this question in an interview that appeared on this website last June Here is what he had to say…

      Q: How long does all this take?
      A: A long time. Scientists often say “5-10 years”. This is just to push expectations somewhere into the future. It depends on money and time given to the task as well as research success. But “10-20 years” is a better and more realistic estimate, and we are 5+ years down that path already, having initiated the HSP Stem Cell Pilot Study in 2008. Our approach is to try to shorten the time frame by first trying to find old drugs that might work with HSP. Because we are using stem cells from people with HSP, we can answer many questions about toxicity early on in the drug discovery process – and previous human usage helps answer these questions as well.

      Q: What stage are we at right now?
      A: We have moved into a new phase of work in 2013 titled Testing and Selecting Therapeutic Drug Candidates for treating HSP. We know what work is required here but there is no way to know how long it will take. We are at the drug discovery stage with some candidate compounds, confirming that they affect HSP stem cell functions and investigating how they do that. If these experiments are a dead-end, then it’s back to the drug-screening step. If successful, we move on to validate the next biological model e.g. iPS cells. That stage is likely to take at least a year, perhaps two, after which we hope to be in a position to move to early-stage clinical trials. This scenario all depends on the success of each step along the way. It will be longer if we have to go back to the drug-screening step. Drug discovery is after all “discovery” and there are risks of failure. Our job as scientists is to use our heads to predict the risks and know success when we see it. In the words of Louis Pasteur: Chance favours only the prepared mind. The speed of discovery depends on people, luck and money.

  15. A large number of my family have this condition, which was passed down from my father’s side of the family. Out of five children, four of us have inherited this condition and two of my three children have also inherited it. I was just wondering would chemotherapy stem cell treatment help this condition like it helps MS patients.

  16. Hi,
    My father has a form of HSP. All of his children (including me) are waiting to get genetic testing. I am 29 and have a one year old toddler. I’m so worried that I might get it and that my child could have it too. Is there any hope of successful treatment options as of yet?
    Thank you for doing this research.

    1. Editor’s note: The stem cell research has led us to be cautiously optimistic about the potential to successfully develop an effective treatment for SPG4 HSP initially. Here is the latest progress report ‘HSP clinical trial program update December 2018‘. You can always find the most recent update on the website homepage. A progress report is published every quarter.

  17. My 27 yr old daughter has hsp, getting worse day by day and can hardly walk. Some doctors are suggesting stem-cell therapy. I need to know how successful it is on these types of patients and what are the alternate treatments and medicines to reduce spasm and pain.

    1. Editor’s note: Stem cell therapy is not an option for treating HSP and has never been attempted to be used for this purpose to the best of our knowledge. Stem cells are very useful as a means of studying HSP and conducting research, but they are not an option for treatment. You need to see your neurologist to determine the best treatments for treating your daughter’s muscle spasm and pain, and allied health professionals such as physiotherapists or occupational therapists to help with her mobility and functionality.

  18. Thank you for your work, I pray everyday for a cure for my 9 year old Granddaughter with HSP type 10 and already in a wheelchair.

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