Promising HSP drugs identified

Potential for future clinical trials


Dr. Yongjun Fan, Simon Weyers, Prof. Mackay-Sim and Gautam Wali
Dr. Yongjun Fan, Simon Weyers, Prof. Mackay-Sim and Gautam Wali

Australian HSP research has identified 2 promising drug candidates with the potential to effectively treat HSP. Further trials are needed this year and next to validate the potential of these drugs as the basis for getting approval for human clinical trials.


This paper reports research proudly supported by this Foundation. Read the full paper.



Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology.

Neurogeneticist Dr. Carolyn Sue
Neurogeneticist Dr. Carolyn Sue

Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking.

Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits.

Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels.

These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport.

From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials.


SOURCE: Biol Open. 2014 May 23. pii: BIO20147641. doi: 10.1242/bio.20147641. [Epub ahead of print] © 2014. Published by The Company of Biologists Ltd. PMID: 24857849 [PubMed – as supplied by publisher]

Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia.

Fan Y1, Wali G1, Sutharsan R1, Bellette B1, Crane DI1, Sue CM2, Mackay-Sim A1.

1National Centre for Adult Stem Cell Research, Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

2Kolling Institute for Medical Research, University of Sydney, Sydney, NSW 2065, Australia.


  1. Biol Open is a world wide publication with highly credentailled parties from all parts of the World involved in assessing articles to be published. This is a significant achievement and would be reasonable to assume that the Australian research into HSP is setting the benchmark. Very exciting news.

  2. Praise the Lord for this wonderful news! I pray that your research will be blessed and that you will truly find the cure for HSP. So many people have waited for so long to hear this news. My heart leaps with joy! Keep up the hard work and I pray that you will be richly blessed.

  3. is this true … i cant blv it … its means my younger brother can walk widut suport he will be cure frm his hsp … can some one please tell from where i can get this medicine .. please help me ,…

  4. Best news we’ve received since our sons diagnosis at age two, he is now twelve! Amazing dedication and hard work from these scientists! Come on clinical trials!!!!

    1. This would be fantastic news if clinical trials became a reality, my daughter also was diagnosed when she was two and she is now 13 yrs old. Everyday I dream of something to come along and cure her!

  5. What a true Blessing this is. God has worked through each and every researcher on this disease and I thank him and them!! Any kind of progress is a Blessing!!!!!

  6. This is the best news I’ve heard in a very long time. I pray that the Lord blesses you all and that soon I can be closer to normal again…not to mention those who have progressed more than myself. You all do an awesome work and I thank you.

  7. This is the best news ever!!! please get the trials on the go! this will mean so much to the people suffering of HSP. it’s the difference between being able to walk or sitting in a wheelchair!

  8. That is aMaZiNg news!!!!! Since the research is being done in Australia, can any of us diagnosed with HSP but not living in Australia (like the USA) volunteer for anything to help (like clinical trials) to help?????? And how do we volunteer?!?

    1. Editor’s Note: The design and location of clinical trials will not likely be known for at least a year. New information will be publicised as it becomes available, and as much equality in access and opportunity to participate in trials as possible will be provided, subject to logistics such as location, time and funding.

  9. Here here Ali, my sister has been diagnosed with this and most of my father’s siblings have had some form of this disease along the way. My father’s mother also had this, I’d love to find out if her English history has a link to Australia, seems like a link between the US and Australia. I would love to volunteer but fortunately I have had no issues at this point but I have three children that I worry about every day. I hope this advances and they find a link to the world and are able to help those who have not yet passed. I watched too many family members struggle and I hate watching my sister go through this too. Thank you all for taking the time to investigate and find help for what seems to be a small margin of people who suffer dearly!

  10. So excited for my daughter. Been such a struggle with HSP causing extreme anxiety together with Diabetes 1. Would be life changing for her and enable her to control the diabetes better.

    1. Editor’s Note: We do not know the answer to that question. The research is focused on SPG4 (Spastin) mutations as they represent about 40% of all HSP incidence, and many times more prevalent than any other form of HSP. There has been some investigation of a group of HSP stem cell samples that are not SPG4, but no other individual mutations are being studied at this time.

  11. How exciting! Thank you Jesus! If not for me…then for future generations who have HSP in their family. I would be willing to be used in clinical trials…but am in United States. Will pray for the studies to be approved for use with humans.

  12. This really is great news but it looks like the clinical trials might not go ahead unless the money can be raised. I intend to set up a regular ongoing monthly donation of $10 towards this and I urge all others to set up a similar ongoing donation. The amount of $10- a month I feel I can handle without hardship, but if that amount is too much, then any regular amount is better than nothing. It is up to us to ensure that this funding is achieved so that the trial can go ahead. I have been told there are over 500 members to this site, if everyone donated $10 a month, that would raise $60,000 a year, $120,000 over 2 years, That’s half way there. Lets all get behind this and make it happen.

  13. When I was tested to find out what kind of HSP I have, the results came back negative. I am just an independent mutation (no actual ‘H’ in my HSP) so who knows what type I really have? I am wondering if I should get my own hopes up, or just settle for being happy for others. Don’t get me wrong; the selfless and brilliant people who have dedicated their lives to this research have my eternal gratitude either way. That said, can I get into the proverbial ‘boat’ or am I waiting still along the shoreline?

    1. Editor’s Note: There is still a long way to go before there is a cure for any form of HSP. How effective any cure for SPG4 HSP might be for other mutations/forms of HSP is unknown at this point. Hopefully there will be sufficient funding in the future to investigate potential cures for other forms of HSP, and indeed similar neurodegenerative diseases, however that will likely depend on how successful the current research program proves to be in coming up with a cure for the SPG4 type.

  14. This is very exciting news! I come from a family with a long history of HSP. I inherited it from my mom, who inherited it from her mom and many uncle’s and second cousins have it a various levels. All seem to be from the SPG4 gene. Now my son was recently tested and he also tested positive for SPG4.

    Here is my ask: How do I get involved in the HSP clinical trial and when is it expected to start?

  15. Hi all, I am one of those affected by HSP. My grandfather, my father and one of my 4 siblings are also affected. My 3 brothers who could be carriers do not have the disease, but can pass it on. If I understand correctly, in 2 years there may be drugs that will cure this disease? If so, millions of thanks to all those who have contributed to make this possible. And encourage them to try to find cures for another 7000 or more minority diseases that exist, like HSP. And if after clinical trials in people, the remedy does not work (I hope with all my heart that if it works) a million thanks anyway, just for trying.

  16. This is very important to my family. My family has a history of HSP, we are from Uruguay. My grandmother inherited it from her father. She was one of four children – two brothers (didn´t inherit it) and two sisters (both did). My aunt and father both inherited it from her. My sister and I still don´t have symptoms but we don´t know if we inherited it or not. My father walks with difficulty trailing his legs due to spasticity (that is why I believe it must be related to SPG4).
    I want to keep in touch in order to follow the news and advances. Thanks

  17. Will this new exciting update be shared with other HSP researchers around the world so they are aware of this new exciting wonderful news! Based in the UK I would like to share this with the HSP staff treating my son in hope that this could be some day be available as a cure. Excellent work carried out!!!.. Would this be available to all ages of people who have HSP (inc. children) as I understand the tests were carried out under Adults with HSP.
    Best news I have heard in ages!

  18. I am praying and hoping these brilliant people from Australia will find the miracle I have been hoping for!

  19. I am from Denmark and also suffer from HSP SPG4. My mutation is extremely rare. I have two questions. Is the type of mutation subordinate in connection with a possible treatment?
    My doctor told me that a possible treatment for my condition will require personalized medicine. Is that correct?
    Kind regards Lars

    1. Editor’s Note: The bottom line is that the answers to your questions are not known at this point in time. The HSP stem cell research has shown that the characteristics of HSP cells that are different from non-HSP cells are largely the same, not only for different SPG4 mutations, but for some non-SPG4 mutations as well. Therefore it is possible that at least some of the different HSP mutations have the same underlying disease mechanism and so may be successfully treated with the same cure. Further research is needed to determine this. Where the underlying disease mechanism is different, further research will be needed to establish the important differences in mechanism and discover different cures. Research into different HSP mechanisms that may exist will likely be facilitated by the knowledge gained in describing and understanding the HSP disease mechanism currently being investigated.

  20. Thank You so much for helping us people with H.S.P. Most of my brothers and one sister have this, tripping, falling. Had this disease since I was 41 years old, now I`m 53 years of age. I long to see a cure for this disease, I hate walking with a cane, I will never get in a wheel chair, my sister did and It`s harder for her to walk now, stiffening legs, joints what have you. I just want to have the clinical trials again, to get back to work what I do, and play some sports. I`m very tired of walking on a cane. I want to be of some help, I`m on Social Security now, but I had a brother pass away in 1995, I had golf tournaments for him because he died of cancer, so I was raising money for cancer Society. Is there any way I could raise money for my disease? Thank You, Donald

  21. posted at 8:00 PM 1/12/15
    I guess I am lucky in one way! I started having problems around 2003. At that time doctors did not know what was going on. I got in touch with a doctor in up state New York. He got me in touch with a doctor at NIH who is doing research on HSP. He said my HSP gene 48 is 1 in 5 in the world that they know of at this time. My last year of teaching kindergarten in 05, I started having problems with walking. Yes, it’s great news about a cure! Where do I find out about the other 4 people that have gene 48. Would like to write to them. ❓

  22. Hi my name is Mary my nephews wife in her early 40 has H.S.P. and it is very hard to watch her suffering. She has really deteriorated over the years and has pain relief administered automatically straight into her spine which has been surgically inserted internally similar to a syringe driver. At the moment she is bed ridden from an infection and is always on some sort of antibiotics and it is taking its toll. If someone could help her participate in a clinical trial would be the best thing, it would give her and her family hope of a normal life.

    1. Editor’s Note: in order to receive communications about clinical trials, the easiest way to ensure that is to be a member of the HSP community served by this Foundation. Go to this link to join up. It is absolutely free and will not cost you a cent, however we strongly encourage giving for 2 reasons – firstly more than $.95 in every dollar given goes directly to fund HSP research to find an effective treatment, including the huge costs of running clinical trials; and secondly, without community member support, research would stop as we receive no government funding whatsoever.

      It is also worth saying, regrettably so, that you should not pin your hopes on participation in a clinical trial leading to a normal life. Clinical trials are not a magic bullet for many reasons. There is a long way to go, and at least a few years before any clinical trials could result in an effective treatment being available. However an effective treatment will be stopping HSP progression as a minimum and hopefully some restoration of function/mobility, but a miracle cure seeing a return to normal life is not foreseeable at this stage. Given the timeline involved and the state of your nephew’s wife’s condition, getting and giving her the best medical treatment available to deal with her symptoms right now is the best that you can do and hope for.

  23. I see that this article is over 8 years old. Has anything happened with the clinical trials? I know the process is slow but we have not heard anything at all. Praying for a cure for this living nightmare.

    1. Editor’s Note: Clinical trials have not commenced. Updates on the research program are published on the website every quarter in the Foundation News section that you can find on the homepage. Here is a link to the latest update For the last 2 1/2 years, the global viral pandemic has disrupted plans to proceed to clinical trials. It has also doubled the pricetag for clinical trials, requiring reassessment of the initiative.

  24. Editor’s note: There is a family run foundation in the US focused on childhood onset SPG4 Their website details the research to find a cure that is going on, where the focus is on gene therapy. It is difficult to say how far progressed or how promising any of this research is as it is all in the pre-clinical investigation stage.
    The Scientific Advisory Board for this Foundation has been asked to develop a strategy for finding a cure for the HSPs. Their initial deliberations indicate that there are significant unknowns, uncertainty and unpredictability about the pathway forward to a cure for any of the HSPs including SPG4.

  25. Where is the main research of finding treatment of hsp/spg4 done? Is the most promising drug gene-therapy? or something else? Who are doing the research?
    Thank you

    1. Editor’s note: There is no good answer to your first question. Nobody knows how far away we are from finding an effective treatment for SPG4. Research efforts are independent, decentralised and poorly publicised to protect intellectual property. It is only after publication that we get a good picture of research efforts that have been undertaken and completed. Where publication does not occur e.g. where research fails, that failure is rarely published and the failed research risks being repeated.
      The most prominent research currently underway is at Drexel University in the US where Peter Baas and his colleagues have received very substantial long-term grants for research on SPG4 from the NIH
      The other prominent initiative is to develop gene therapies for children with de-novo mutations in the SPAST gene and this is also happening in the US

      Regarding drug and gene therapy, good arguments are made for pursuing both forms of treatment as there are pros and cons of each. When success is finally achieved, it is reasonable to expect more clarity on this question.

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